José Rodríguez-Espinosa

Deleterious effects of glucocorticoid replacement on bone in women after long-term remission of Cushing's syndrome.

Endogenous hypercortisolism and high‐dose and long‐term glucocorticoid (GC) therapy reduce bone mass. Patients in remission after successful treatment of Cushings syndrome (CS) often present hypoadrenalism and require long‐term GC replacement. The aim of our study was to evaluate whether this GC “replacement” had any further effect on bone in women after long‐term remission of CS. Thirty‐seven women (mean age: 50 ± 14 yr; 27 of pituitary and 10 of adrenal origin) with cured CS (mean time of cure: 11 ± 6 yr), 14 with active CS, and 85 sex‐, body mass index (BMI)‐, and age‐matched controls were enrolled. BMD and BMC were measured by DXA scanning. Bone biochemical markers were also measured. Duration and dose of GC replacement and duration of endogenous hypercortisolism were calculated. Cured and active CS patients had less BMC, BMD, and osteocalcin than controls (p < 0.01). These differences were observed in estrogen‐sufficient women but not in those with estrogen deficiency. Duration of GC treatment (mean: 42 mo; range, 2–420 mo) and endogenous hypercortisolism (mean: 70 mo; range, 13–241 mo) negatively correlated with BMC and lumbar spine BMD. After regression analysis, the main predictor of abnormal BMC and BMD was the duration of GC replacement (p < 0.01). Patients treated for CS persistently have less bone mass despite long‐term cure. Both duration of endogenous hypercortisolism and mainly exogenous “replacement” therapy with GC negatively affect bone mass. Thus, the additional deleterious effect of GC for the treatment of adrenal axis suppression should be considered.

Thyroid hemiagenesis in two sisters

Two sisters with thyroid hemiagenesis are described. The patients presented diffuse thyroid enlargement of right lobe. The left lobe and isthmus were absent and thyroid scans were similar in both cases. The patients were clinically euthyroid. Basal serum thyroid hormones and TSH were within normal range, but TSH response to TRH administration was exaggerated in both patients. The finding of familial occurrence and the same functional and morphological characteristics of remnant thyroid tissue in both cases suggest a genetic determination for this abnormality.

The role of matching menstrual data with hormonal measurements in evaluating effectiveness of postcoital contraception.

The effectiveness of postcoital contraception can only be estimated. The most commonly used method of calculation compares the expected pregnancy rate in the exposed population to the resultant pregnancies after treatment. Estimation of the fertile period and the day of ovulation are critical to calculate the expected pregnancies. The aim of this study was to improve the accuracy of calculations by evaluating the hormonal status on the day of contraceptive treatment. A total of 483 consecutive women requesting postcoital contraception was included in a prospective observational trial. A blood sample was obtained at the moment of consultation to measure serum luteinizing hormone, estradiol, and progesterone concentrations. An ethinylestradiol-levonorgestrel combination (100 micrograms/500 mg for two doses, 12 h apart) was then prescribed. The fertile period was estimated according to previous hormonal studies in the normal cycling population. Of 483 women, 64 (13.25%) women were excluded because they presented irregular menstrual cycles and 37 (7.6%) women were lost to follow-up. Two pregnancies occurred in the remaining 382 women. Following Wilcoxs and Trussells methods, 21.1 and 17.75 pregnancies should be expected, yielding an overall treatment effectiveness of 90.52% (95% confidence interval [CI] 62.58%-97.6%) and 88.73% (95% CI 55.93%-97.12%), respectively. Hormonal data were available in 356 women; 303 of whom presented with regular cycles. Hormonal information in this group restricted the number of exposed cases to 88 women. Of the women included in Trussells method of analysis, only 51 (51.5%; p < 0.05) were at risk using hormonal data. Fifty-six percent (95% CI 34.9%-75.6%) of women with luteinizing hormone levels > 20 IU/L were not between days-1 and +1 of the cycle. Hormonal studies suggest that methods based on pregnancy risk calculated by cycle day do not faithfully reflect the real exposure.

Use of somatostatin analogue scintigraphy in the localization of recurrent medullary thyroid carcinoma

Abstract.Detection of recurrence of medullary thyroid carcinoma (MTC) remains a diagnostic problem. Increased serum tumour marker levels frequently indicate recurrence while conventional imaging techniques (CIT) are non-diagnostic. In this study, we performed indium-111 octreotide scintigraphy and CIT in a series of 20 patients with MTC presenting with elevated serum tumour markers after surgery. 111In-octreotide whole-body studies detected 15 pathological uptake foci in 11 of the 20 patients studied and CIT detected 17 lesions in 11 of the 20 patients. Ten patients underwent reoperation, five of them with positive 111In-octreotide scintigraphy and CIT and two with positive isotopic exploration and negative CIT. Surgical findings demonstrated that the results of isotopic study and CIT had been false-positive for MTC in one case (sarcoidosis). The six patients with true-positive 111In-octreotide studies had significantly higher basal calcitonin (CT) and carcinoembryonic antigen (CEA) levels than the patients with negative isotopic studies. The expression of somatostatin receptor (SSTR) subtypes by PC-PCR could be investigated in four cases with a positive isotopic study. Among the three cases with a true-positive study, SSTR2, the SSTR subtype that preferentially binds to the somatostatin analogue octreotide, was detected in two, SSTR5 was demonstrated in the three, and SSTR3 was detected in one. No subtype of SSTR was detected in the case with a final diagnosis of sarcoidosis. We conclude that 111In-octreotide has limited sensitivity in detecting recurrence in patients with MTC, although its sensitivity may improve with high serum CT levels. This radionuclide imaging technique should be employed when conventional imaging techniques are negative or inconclusive or when the presence of somatostatin receptors may provide the basis for treatment with somatostatin analogues.

A novel germline mutation in exon 5 of the multiple endocrine neoplasia type 1 gene

Abstract The autosomal dominant multiple endocrine neoplasia type 1 (MEN1) syndrome is characterized by neoplasia of parathyroids, anterior pituitary, and gastrointestinal and pancreatic neuroendocrine tissues. Recently the gene responsible for the MEN1 syndrome has been identified on chromosome region 11q13. Most of the described mutations are nucleotide substitutions and small deletions affecting exons 2 and 3, causing protein truncation. Only one mutation in exon 5 has been found, and this corresponds to a MEN1 sporadic case. Small insertions are also rare. We studied a MEN1 family composed of five members, two of whom were clinically affected. We found a new germline 1 basepair insertional mutation affecting the exon 5 of the MEN1 gene in the two members affected in this MEN1 family.

Prevalence of Metabolic Syndrome Among Human Immunodeficiency Virus–Infected Subjects Is Widely Influenced by the Diagnostic Criteria

BACKGROUND The aim of this study was to compare the prevalence of metabolic syndrome in human immunodeficiency virus (HIV)-infected patients treated with highly active antiretroviral therapy (HAART), using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), European Group for the Study of Insulin Resistance (EGIR), and International Diabetes Federation (IDF) definitions. METHODS A cross-sectional study was carried out with 159 consecutive adult HIV-infected subjects (120 males and 39 females) under HAART. Anthropometric and laboratory parameters were measured by standard methods. Hyperinsulinemia was defined by a fasting concentration >75th percentile of values obtained in healthy individuals (107.5 pmol/L). RESULTS The prevalence of ATP III-defined metabolic syndrome was 10.1%; it was 28.3% according to EGIR criteria and 15.1% using the IDF definition. The concordance between the definitions was low (kappa coefficient ranging between 0.134 and 0.296). All subjects with EGIR-defined metabolic syndrome had hyperinsulinemia, but only 50% of those with ATP III-defined metabolic syndrome and 62.5% in the IDF metabolic syndrome population had hyperinsulinemia. CONCLUSIONS The inclusion of hyperinsulinemia as a criterion in the EGIR metabolic syndrome definition made it more discriminative than the ATP III definition, both in men and women, and than the IDF definition in men to identify metabolic syndrome in HIV-infected subjects under HAART.

Antibody binding serum T3 in a patient with hepatocarcinoma

Thyroid hormone levels were studied in a euthyroid patient with hepatocellular carcinoma. The thyroid gland was normal at autopsy and both antithyroglobulin and antimicro-somal antibodies were undetectable in serum. Serum triiodothyronine (T3) values as measured by different RIA procedures, showed striking discrepancies suggesting the presence of an endogenous T3 binding antibody. The preincubation of the patient’s serum with 125I-T3, followed by a precipitation with polyethyleneglycol showed a 74.8% of binding, confirming the presence of an endogenous factor interfering with T3 assays. Agarose electrophoresis of the patient’s serum showed that 125I-T3 migrated mainly with the gammaglobulin fraction (60%). When immuno-precipitation tests with different antihuman antiimmunoglobulins were carried out, a positive binding for immunoglobulin G (11.9%), Fab (8.5%) and lambda chain (9.3%) was noted. Scatchard plot analysis showed a binding affinity of 0.77 × 109 liter/mol and a binding capacity of 1.02 nmol/liter. These data suggest that the abnormal serum T3 binding was caused by the presence of a T3 antibody which was shown to be an immunoglobulin G specific only for the lambda chain.

Falsely increased prostate-specific antigen concentration attributed to heterophilic antibodies.

We describe a 50-year-old man with a serum total prostatic-specific antigen concentration of 67.6 µg/L (reference range 0-4 µg/L) revealed as part of an annual health check programme. Clinical examination failed to identify any prostatic abnormality, and laboratory investigation indicated positive interference due to heterophilic antibodies.

DOES TESTOSTERONE INFLUENCE THE POST‐STIMULATORY LEVELS OF CALCITONIN IN NORMAL MEN?

We have analysed the sex difference of calcitonin (CT) levels after combined stimulation with calcium and pentagastrine (Ca‐PG) in the normal population, and the relationshp of the post‐stimulatory CT levels with free testosterone (FT). We have also studied the correlation between CT values and the anthropometric parameters, body mass index (BMI) and body surface area (BS), as well as the relationship between CT levels and calcium. A positive and statistically significant correlation was found between post‐stimulatory CT and the increment over the base‐line of CT and basal FT, and with the anthropometric parameters. However, the increment of CT and the peak values of CT did not have any significant correlation with the Ca levels (basal or post‐stimulation). We conclude that the enhanced CT response found in normal men compared to normal women is at least partially determined by the higher testosterone levels found among normal men.

Molecular Pathology of Multiple Endocrine Neoplasia Type I: Two Novel Germline Mutation; and Updated Classification of Mutations Affecting MEN1 Gene

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined development of tumors in several endocrine glands and other tissues. The MEN1 gene was recently identified and isolated by positional cloning. This gene was screened in two unrelated MEN1 Spanish kindreds (with four affected members and seven asymptomatic members) using single-strand conformation polymorphism, DNA sequencing, and restriction enzyme analysis. Two novel germline mutations were identified: a missense in exon 2 (H139R) and a splice-site in intron 9 (1461-2A>C). These findings allowed us to identify the MEN1 carriers among the seven asymptomatic members analyzed. An updated review of the mutations and polymorphisms found in the analysis of the MEN1 gene is provided. The report of all germline mutations causing MEN1 and easy access to this updated information are both of special diagnostic interest, because this greatly facilitates the task of attributing the disorder to a specific mutation found in a given MEN1 family. This is especially helpful in the critical differentiation of missense mutations from nonsynonymous polymorphisms that fit the pattern of segregation of the disease, but do not cause it.