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Adult hypopituitary patients with growth hormone deficiency (GHD) show a significant decrease in bone mass and an increased fracture rate. Replacement therapy with GH increases bone turnover. Most of the long-term data on bone mineral content (BMC) and bone mineral density (BMD) have been acquired in open, noncontrolled trials involving limited numbers of patients. To determine whether long-term GH therapy is beneficial for bone despite the increased bone turnover, 100 patients (59 men and 41 women), aged 25-65 years (mean, 49.7 years) with adult-onset GHD were randomized to treatment with GH (40 men and 28 women; mean dose, 0.18 IU/kg per week) or to a nontreated control group (19 men and 13 women) for 24 months. Despite a similar increase in parameters of bone turnover (osteocalcin [OC], procollagen type I carboxy-terminal propeptide [PICP], and pyridinolines ([PYD]) in male and female GH-treated patients compared with controls, the effects on BMC and BMD as evaluated by dual-energy X-ray absorptiometry were gender specific. A significant increase in spine BMC and BMD and total hip BMD and a decrease in BMD at the ultradistal radius over time was observed in male GH-treated patients compared with the evolution in controls (mean +/- SEM change at 24 months: +6.8 +/- 1.1% and p = 0.009, +5.1 +/- 0.8% and p = 0.005, +3.5 +/- 0.7% and p = 0.02, and -2.6 +/- 0.8% and p = 0.008, respectively). No significant treatment effects were observed in female patients. Despite the increase in the total remodeling space induced by GH treatment, prolonged GH therapy in adult-onset GHD has a positive effect on bone balance, maintaining bone mass in women, and even increasing it in men over a 2 year-period.

Cabergoline is a new long-acting dopamine agonist that is very effective and well tolerated in patients with pathological hyperprolactinemia. The aim of this study was to examine, in a very large number of hyperprolactinemic patients, the ability to normalize PRL levels with cabergoline, to determine the effective dose and tolerance, and to assess the effect on clinical symptoms, tumor shrinkage, and visual field abnormalities. We also evaluated the effects of cabergoline in a large subgroup of patients with bromocriptine intolerance or -resistance. We retrospectively reviewed the files of 455 patients (102 males and 353 females) with pathological hyperprolactinemia treated with cabergoline in 9 Belgian centers. Among these patients, 41% had a microadenoma; 42%, a macroadenoma; 16%, idiopathic hyperprolactinemia; and 1%, an empty sella. The median pretreatment serum PRL level was 124 μg/L (range, 16–26,250 μg/L). A subgroup of 292 patients had previously been treated with bromocriptine, of which 140 showed bromocriptine intolerance and 58 showed bromocriptine resistance. Treatment with cabergoline normalized serum PRL levels in 86% of all patients: in 92% of 244 patients with idiopathic hyperprolactinemia or a microprolactinoma and in 77% of 181 macroadenomas. Pretreatment visual field abnormalities normalized in 70% of patients, and tumor shrinkage was seen in 67% of cases. Side effects were noted in 13% of patients, but only 3.9% discontinued therapy because of side effects. The median dose of cabergoline at the start of therapy was 1.0 mg/week but could be reduced to 0.5 mg/week once control was achieved. Patients with a macroprolactinoma needed a higher median cabergoline dose, compared with those with idiopathic hyperprolactinemia or a microprolactinoma: 1.0 mg/week vs. 0.5 mg/week, although a large overlap existed between these groups. Twenty-seven women treated with cabergoline became pregnant, and 25 delivered a healthy child. One patient had an intended abortion and another a miscarriage. In the patients with bromocriptine intolerance, normalization of PRL was reached in 84% of cases, whereas in the bromocriptine-resistant patients, PRL could be normalized in 70%. We confirmed, in a large-scale retrospective study, the high efficacy and tolerability of cabergoline in the treatment of pathological hyperprolactinemia, leaving few patients with unacceptable side effects or inadequate clinical response. Patients with idiopathic hyperprolactinemia or a microprolactinoma, on average, needed only half the dose of cabergoline as those with macroprolactinomas and have a higher chance of obtaining PRL normalization. Cabergoline also normalized PRL in the majority of patients with known bromocriptine intolerance or -resistance. Once PRL secretion was adequately controlled, the dose of cabergoline could often be significantly decreased, which further reduced costs of therapy.

Malignant prolactinomas are extremely rare (1, 2). The diagnosis of these carcinomas is mainly based on the patient’s medical history and the detection of metastases. Nuclear medicine offers new imaging modalities for the detection of metastases of pituitary carcinomas. These techniques may have serious consequences for subsequent investigations and therapy. The case presented here shows the clinical behavior of a malignant prolactinoma. The usefulness of dopamine D2 receptor scintigraphy for establishing the diagnosis and subsequently directing the therapeutic approach is illustrated.

SUMMARY Apart from genes in the HLA complex (IDDM1) and the variable number of tandem repeats in the 5′ region of the insulin gene (INS VNTR, IDDM2), several other loci have been proposed to contribute to IDDM susceptibility. Recently, linkage and association have been shown between the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) gene on chromosome 2q and IDDM. In a registry-based group of 525 recent-onset IDDM patients

HMG-CoA reductase inhibitors have been proven effective in decreasing the plasma cholesterol levels in patients affected with various forms of hypercholesterolemia, familial dysbetalipoproteinemia, familial combined hyperlipidemia and in nephrotic and diabetic dyslipidemia. The purpose of this study was to monitor and evaluate the efficiency and safety of the therapy with simvastatin, an HMG-CoA reductase inhibitor, in a group of patients treated by continuous ambulatory peritoneal dialysis (CAPD) with severe hypercholesterolemia. Monitoring of the changes occurring in the various lipids and apolipoproteins in these patients included the measurements of the plasma lipids and apolipoproteins A-I, A-II, B, C-II, A-IV and Lp(a). Lipoproteins were separated by gel filtration, on a Superose 6HR column, before and after 24 weeks of treatment. The patterns were compared to those observed in a group of primary hyperlipidemic patients treated with Lovastatin, a compound of the same class. The drug was well tolerated by the CAPD patients and no adverse reaction was observed. In addition to the decrease of the total and LDL cholesterol, similar to that reported in other groups of patients, we further observed a decrease of the apo E concentration in both the CAPD and the hyperlipidemic patients. This decrease was especially pronounced in the HDLE fraction and could involve an upregulation of the apo B-E and/or apo E receptor. These results should provide information about the mechanism of action of this drug in patients with end-stage renal disease.

Varicocele is the most frequent cause of male subfertility. Several invasive and noninvasive techniques can be used to visualize scrotal phlebectasies. In this study sequential scintigraphy after intravenous injection of 99mTc-albumin was compared with tele-thermography. The normal and pathological images are described. The more obvious the clinical condition, the more lesions were revealed by scintigraphy (29.6% in subfertile men suspected of having variococele; 76.9% in patients with first degree varicocele; and 100% in Grades II and III cases). In 55 cases (of a total of 76 cases explored by radioisotopic techniques), the comparison of the thermographic results with the scintigraphy results suggests that scrotal scintigraphy is less sensitive. However, there are more false positive thermographies expressed as a discordance with clinical examination, which indicates higher specificity of scintigraphy. In conclusion scrotal scintigraphy cannot be considered as the screening procedure of first choice for varicocele, but it can give complementary information, especially when thermographic results are at variance with the clinical examination.

Steroid metabolism in hepatoma tissue culture (HTC) cells derived from a male rat was investigated. Steroids in ethanol were incubated with the cells for various lengths of time. Volume of ethanol never exceeded 1% of incubation volume. Thin-layer and paper chromatography were used. Incubation was with tritiated steroids. It was demonstrated that testosterone as well as dihydrotestosterone is transformed. The main enzyme activities detected were 5alpha-reduction and 3alpha-, 3beta, and 17beta-hydroxysteroid dehydrogenation. The pattern of metabolism was reproducible and varied with time, substrate concentration, and number of cells incubated. Some steroids interfered with androgen metabolism. 17beta-estradiol, 17-epitestosterone, and progesterone competed for the 17beta-hydroxyprogesterone dehydrogenase. it is concluded that 3beta and 17beta reduction in the HTC cells may be catalyzed by the same enzyme which might differ considerably from the 3beta-hydroxysteroid dehydrogenase assayed in intact liver cells. A hepatoma derived from a female rat also produced considerable amounts of 3beta-derivatives of testosterone.

Measurements of receptor concentration and enzyme activities in cultured fibroblasts derived from skin biopsies should faithfully reproduce genetically determined donor characteristics. In the present study, we investigated whether and how selection of ligands or passage number influences such measurements. Receptor binding has been compared in a series of normal human skin fibroblast lines afterincubation with 1 nM [3H]- testosterone or [3H]5a-dihydrotestosterone [3H]DHT. In most cell lines, higher binding capacities were noted after incubation with DHT than after incubation with testosterone. In some lines, the reverse was observed. Evidence is presented that even after incubation with testosterone, DHT was the major compound bound to the receptor protein. Moreover, a clear-cut correlation could be demonstrated between 5a-reductase activity and receptor binding estimated from incubations with testosterone. The fact that in some cell lines estimates of binding capacities derived from studies wit...

A case is reported of a hypercalcemic patient with primary Addison's disease. A combination of increased calcium input into the extracellular space and reduced calcium removal by the kidney accounted for the hypercalcemia. The mechanisms responsible for the reduction in calcium removal were decreased glomerular filtration and increased tubular calcium reabsorption. Both renal factors were secondary to volume depletion and improved rapidly during rehydration with saline infusion. The enhanced calcium mobilization was probably of skeletal origin. It persisted irrespective of volume status until hydrocortisone treatment was instituted. Serum 1,25-dihydroxyvitamin D3 levels were below 10 pg/ml, even after normalization of the glomerular filtration rate, but returned slowly to the normal range during corticosteroid substitution. Serum 25-hydroxyvitamin D3 and parathyroid hormone levels were within the normal range. Our case report therefore demonstrates that physiological amounts of glucocorticoids reduce bone resorption, normalize serum calcium, and restore the production of 1,25-dihydroxyvitamin D3.

1. 1. Purified nuclei were prepared from various organs and brain regions of rats. The preparations were assayed for 5α-reductase activity, and checked for purity by measurement of RNA-DNA ratios. Although prostatic nuclei showed the highest 5α-reductase activity, the other nuclear fractions were also able to reduce testosterone into its active metabolite: 17β-hydroxy-5α-androstan-3-one. In all tissues, however, the nucleus-associated 5α-reductase activity was inversely related to the purity of the nuclear fractions. 2. 2. Prostate, kidney, submaxillary gland, lung and midbrain were completely fractionated. Total 5α-reductase activity varied as follows: lung > prostate > kidney > submaxillary gland > midbrain. The particulate fractions were the major sites of 5α-reductase activity in all tissues except for the submaxillary gland. The nuclear fraction reached 19% of the total 5α-reductase activity in the kidney and 25% in the prostate. 3. 3. The low apparent K m of the 5α-reductase for testosterone reported in prostatic nuclei was also found in lung nuclei (1.56 μM) and kidney nuclei (0.96 μM). 4. 4. It is concluded that the androgen responsiveness of a particular tissue cannot be accounted for by any of the parameters of 5α-reductase activity studied: the occurrence of an enzyme with particularly high affinity for testosterone, the total cellular activity, or the absolute or relative amount of this activity associated with purified nuclei.

Radionuclide imaging with Tc-99m-pertechnetate in a patient with a mixed papillary-follicular carcinoma of the thyroid gland showed evidence of increased radioactivity at sites of functioning metastases. The use of Tc-99m-pertechnetate as well as I-131 for imaging in search of functioning thyroid metastases is discussed.

In otherwise normal and healthy young men the most frequent cause of subfertility is varicocele. As this is also the cause most easy to cure, correct diagnosis of varicocele is extremely important.

Publisher Summary This chapter discusses the differentiation in steroid metabolizing enzymes and the intracellular steroid binding organized by fetal and/or neonatal early testosterone secretion. Many mammalian organs or structures initially display both male and female potentialities but have a fundamental tendency to become female. In males, successive factors impose regression upon some of these female potentialities. Testosterone, or a steroid (estrogen) derived from it, is the regression factor acting in the brain, the mammary anlagen and probably also in other parts of the organism. Some of the processes of regression could be because of destruction of receptors for estradiol; others seem to imply atrophy of cells. On the other hand, early testosterone seems responsible for a score of changes whereby male potentialities are developed. This development finds its expression in the selective growth of organs and cell populations, or in the induction of intracellular components such as steroid metabolizing enzymes or androgen receptors. Some of the latter changes could facilitate the later action of testosterone and render specific parts of the body more sensitive to its action.