Haemochromatosis presenting with loss of libido and impotence.

Haemochromatosis may present in different ways according to the organ predominantly affected by iron overload. Presentation with symptoms caused by deficiency of pituitary gonadotrophins is recognized but rarely reported. We present such a case and argue that haemochromatosis may be a more common cause of impotence than is presently realized.

Is preoperative localisation of insulinomas necessary?

During the past 20 years 33 patients suspected of harbouring an insulinoma have been investigated. 29 had laparotomy, and tumours were removed from 27.2 of the 29 and 1 other proved not to have an insulinoma, although preoperative imaging had suggested a tumour. Four different localisation procedures were used, and in some patients more than one technique was applied. Selective arteriography of branches of the coeliac axis showed the position of the insulinoma correctly in 9 out of 18 cases, but in all of these the tumour was felt at operation, so that the information provided was unnecessary. Arteriography gave false localisation in 4 patients and missed the tumour completely in 4 but was also negative in 1 patient not harbouring a tumour. Ultrasonic examination provided correct localisation in only 2 out of 11 instances and computer-assisted tomography in 1 out of 8. Insulin estimation in blood obtained at percutaneous transhepatic portal-venous sampling (THPVS) provided correct localisation in 2 out of 8 cases, but in only 1 of these was it needed to guide pancreatic resection. Localisation was spurious in 5 patients, and in 1 there was no evidence of a tumour at all. In 23 patients the surgeon felt and removed the insulinoma at the first operation. In 3 tumour was palpable at a second laparotomy some years later. In only 1 was no tumour felt at operation. The false-positive findings in the THPVS were caused by misinterpretation of data. For a peak of insulin concentration in the portal vein to be meaningful, it should exceed 200 mU/l and to be fully diagnostic it should be greater than 500 mU/l. Present imaging techniques are not precise enough to localise an insulinoma. An experienced surgeon has a very high probability of being able to palpate the tumour at operation, and preliminary localisation is therefore not needed in most cases.

Investigation of the usefulness of the plasma adenosine 3' 5' - cyclic monophosphate response to glucagon in thyroid disease.

The plasma adenosine 3', 5' - cyclic monophosphate (cyclic AMP) response to 50 micrograms of intravenous glucagon was examined in 14 normal euthyroid subjects, 15 patients with thyrotoxicosis and 5 patients with myxedema. The cyclic AMP responses to 50 micrograms of intravenous glucagon was significantly higher in the hyperthyroid group than in the euthyroid or hypothyroid group. However, the areas of overlap between all three groups were large and there was little relationship between the plasma cyclic AMP response to glucagon and the biochemical assessment of thyroid function. Serial studies of the response to 50 micrograms glucagon were carried out in four patients receiving treatment for thyrotoxicosis. Again, there was not consistent relationship between the plasma cyclic AMP responsiveness to glucagon and the free thyroxine index. It is concluded that although the plasma cyclic AMP response to glucagon is increased in thyrotoxicosis and decreased in myxedema, the variability of this response in thyroid disease precludes its use as a tissue index of thyroid hormone responsiveness.

The role of autonomic neuropathy in diabetic foot ulceration.

In an attempt to define the role of autonomic neuropathy in the pathogenesis of diabetic foot ulcers, we have studied diabetic patients with and without ulcers, and a group of non-diabetic controls. A series of standard autonomic function tests have been compared with measurement of the Galvanic Skin Response (GSR). Patients with foot ulcers showed evidence of more severe somatic and autonomic neuropathy than diabetic subjects with no ulcer. The GSR was found to correlate well with the more conventional tests. In addition it proved to be abnormal more often than any other test for autonomic neuropathy in the diabetic patients with foot ulcers. In a preliminary follow-up study 2 patients with an abnormal GSR but no ulcer at the time of testing have subsequently acquired plantar ulcers. It is suggested that the GSR may prove to be a useful means of detecting diabetic patients at risk from foot ulceration.

Decrease of antibodies to insulin, proinsulin and contaminating hormones after changing treatment from conventional beef to purified pork insulin.

The sera of 30 patients who had been treated with conventional beef insulin were tested for binding of insulin and other pancreatic hormones. All showed antibody binding of insulin, 29 binding of proinsulin, 29 binding of pancreatic polypeptide, two binding of glucagon but none of the sera bound vasoactive intestinal peptide or somatostatin. After changing therapy to highly purified pork insulin the binding capacity of sera for insulin and the other hormones was monitored for up to 35 months and a steady fall was found in nearly all cases. In eight of the patients conventional beef insulin treatment was resumed: in one month binding of insulin and of the other hormones increased back to the initial levels. In eighteen subjects who had only received highly purified pork insulin low levels of insulin binding were found with no binding of proinsulin or other hormones. The amounts of proinsulin and contaminating hormones in highly purified pork insulin are so low that they are not immunogenic; conventional beef insulin not only contains immunogenic amounts of proinsulin and the contaminating hormones pancreatic polypeptide and glucagon but also is more immunogenic than purified pork insulin.

Measurement of the integrated concentration of prolactin in normal subjects and patients with hyperprolactinaemia.

To determine whether the fluctuations in the concentration of prolactin in plasma of man affect diagnostic procedures, the integrated concentration of prolactin has been compared with a basal concentration. A continuous sampling apparatus was used to study nine normal subjects and 12 subjects with features of the hyperprolactinaemia syndrome. Small differences were demonstrated, which were, however, neither statistically significant nor likely to influence clinical decisions. It is concluded that single estimations of the concentration of prolactin in blood, taken under resting conditions, are adequate for routine diagnostic use.

Oral testosterone, a reappraisal.

A microparticulate form of free testosterone was given orally to 6 hypogonadal men. Plasma levels were followed after a 200-mg dose, and a double-peak effect was observed. This suggests that particles of different sizes were absorbed at different rates. The clinical and biochemical effects were observed over a 2-month period, on a dose of 200 mg twice daily, taken in place of the usual androgen replacement. The results indicate that absorption is not sufficiently reliable for routine use. The large doses required to achieve therapeutic levels, make oral administration of free testosterone impractical.

Measurement of the 24 hour integrated plasma concentration of growth hormone, in assessing the response of acromegalic patients to treatment.

The integrated concentration of growth hormone (ICGH) has been measured in fourteen acromegalic patients, and compared with the basal plasma growth hormone concentration (BGH). Seven patients were treated by trans-sphenoidal pituitary surgery, and in these, similar percentage reductions of BGH and ICGH occurred after treatment. The other seven patients were treated with bromocriptine alone, and in these the percentage reduction of ICGH was significantly less than that of BGH. Measurements of basal plasma growth hormone concentration may be unreliable in assessing the response of acromegalic patients to treatment with bromocriptine. The ICGH can be measured easily on a single blood specimen obtained by continuous sampling over 24 h, and may be more reliable for this purpose.

Insulin binding capacity in patients changed from conventional to highly purified insulins. An indicator of likely response.

Highly purified insulins offer the possibility of reducing insulin antibody levels and insulin requirement. Those likely to respond cannot be predicted on clinical grounds and a simple laboratory test is recommended for this purpose. This is based on insulin binding capacity (IBC) of plasma and has been used to follow a group of 47 patients over six months. 47 patients previously treated with British soluble and isophane insulins were changed to highly purified Leo Neutral and Leo Retard. 36 showed a reduction of insulin requirement and two groups could be identified. An IBC of greater than 40 muU/ml was associated in 94% with a reduction of insulin dose; if the IBC was less the response was unpredictable. The initial IBC was related to the initial insulin requirement and to the eventual percentage reduction. Serial measurements in patients with high initial IBC showed a steady fall. Measurement of the IBC is a simple investigation; if the level is greater than 40 muU/ml changing to a highly purified insulin is likely to be associated with reduction of insulin requirement.

Effect of insulin antibodies on free and total plasma-insulin.

Insulin administration often causes the development of insulin antibodies. Plasma insulin-binding capacity was assessed and free and total plasma insulin were measured in 96 insulin-dependent diabetic patients. Patients with the highest insulin binding capacity not only had the highest total insulin but also had the lowest free insulin. It is concluded that bound insulin is not unavailable to cells, that sufficient dissociation can occur for this insulin source to make a sizeable contribution to insulin delivery to the cell receptors, and that this can happen at a very low free insulin concentration.