Enrico Pucci

Percutaneous ethanol injection treatment of autonomous thyroid adenoma: hormonal and clinical evaluation

OBJECTIVE We have evaluated the efficacy of percutaneous ethanol Injection as an alternative to surgery and iodlne‐131 treatment in solitary autonomous thyroid adenoma.

Prolonged treatment of hirsutism with flutamide alone in patients affected by polycystic ovary syndrome

Hirsutism is a common symptom of women affected by polycystic ovary syndrome (PCOS). The effectiveness of the antiandrogen flutamide alone was studied in 25 patients affected by PCOS with severe hirsutism for a period of 24 months. Seventeen of these patients had not been treated before and eight had had previous but unsatisfactory therapy. Nineteen patients showed a normal body weight (BMI < 25 kg/m2) whereas six were obese (BMI > 35 kg/m2). A chemical and endocrinological evaluation and an assessment of the degree of hirsutism, assigned by Ferriman-Gallwey score (mean 22 +/- 3.038), was performed under baseline conditions. Patients started treatment with flutamide (Eulexin, Schering-Plough, Kenilworth, USA) at the dose of 500 mg daily. A chronobiological assessment of gonadotropin episodic secretion and of gonadotropin response to GnRH challenge (10 micrograms in bolus) was done before and on day 7 of flutamide administration. During treatment, our patients showed a marked and significant reduction of hirsutism starting from a score of 6 and reaching the maximum (9.6 + 2.1) at 24 months of therapy. No relevant hormonal changes or side-effects were observed during therapy. Our data demonstrate that hirsutism in PCOS can rapidly and markedly respond to treatment with flutamide alone without important side-effects even if administered for a long period.

Clinical characteristics and genetic analysis in women with premature ovarian insufficiency.

OBJECTIVE Premature ovarian insufficiency (POI) is defined as a primary ovarian defect characterized by absent menarche (primary amenorrhea) or premature depletion of ovarian follicles before the age of 40 (secondary amenorrhea) with hypergonadotropism and hypoestrogenism. METHODS We studied the clinical, biological, and genetic data related to 50 POI patients with a mean age of menopause of 29 years (94% with secondary amenorrhea, 6% with primary amenorrhea and 15% with a family history of POI). Seventeen patients were affected by endocrine autoimmune diseases, antral follicles were observed in 31 patients by ultrasonography. RESULTS Karyotype analysis did not show any abnormality of the X chromosome. No mutation in FSH receptor and GDF-9 genes was reported, while in one patient a variant of BMP-15 gene (A180T) was found. Four patients had fragile X mental retardation 1 gene (FMR1) premutation and one an intermediate sized CGG repeats of the same gene. Two patients with FMR1 premutation were sister and developed secondary amenorrhea at the age of 34 and 37 years. The other two patients presented with oligoamenorrhea at the age of 39 and 34 years. The patient harboured the intermediate sized CGG repeats developed secondary amenorrhea at the age of 33 years. CONCLUSIONS The genetic analysis performed on a cohort of patients with POI revealed that 8% had FMR1 premutation and only one patient a previously known variant of BMP-15 gene. No alteration of the karyotype and FSH receptor and GDF-9 genes was evidenced.

Gonadotrophin receptor blocking antibodies measured by the use of cell lines stably expressing human gonadotrophin receptors are not detectable in women with 46,XX premature ovarian failure

background  Premature ovarian failure (POF) is defined by cessation of ovarian function after puberty and before the age of 40. The syndrome is characterized by amenorrhoea, oestrogen deficiency and elevated levels of gonadotrophins. Autoimmunity has been proposed as a mechanism for some cases of destruction or malfunction of ovarian follicles. POF is often associated with type I and type II polyglandular autoimmune syndromes. It has also been postulated that receptors such as the LH and FSH receptors might become targets for blocking antibodies and such antibodies could be a cause of ovarian failure.

Serum PSA levels are not affected by the menstrual cycle or the menopause, but are increased in subjects with polycystic ovary syndrome

Background/aims: Prostatic specific antigen (PSA) is the most specific prostatic tumor marker in man. Recently, PSA has been detected in a variety of tissues and fluids in women, and its determination suggested as a marker of hyperandrogenism. However, precise information about the physiology of PSA in females is not available. The goal of this study was to assess serum concentrations of PSA in healthy pre-menopausal women (healthy pre-menopausal group), menopausal women (menopause group) and patients with polycystic ovary syndrome (PCOS group). Methods: PSA, androgens, LH, FSH, 17-β-estradiol (E2), progesterone (Pg) were assessed in 40 post-menopausal women, 35 fertile controls and 35 women with PCOS. Results: No significant difference in PSA concentrations could be demonstrated in different phases of the menstrual cycle in healthy pre-menopausal group and between pre- and post-menopausal groups. No correlations could be demonstrated between serum PSA levels and the following parameters: age, body mass index (BMI), LH, FSH, E2, testosterone (T), DHEAS, and SHBG, both in pre- and post-menopausal women. Significantly higher PSA levels (median=14 pg/ml) were found in the PCOS group compared to both pre-menopausal (median=5 pg/ml) and menopausal (median= 5 pg/ml) groups (p<0.05). Conclusions: only minor fluctuations of serum PSA concentrations are observed in healthy pre- and post-menopausal women, while serum level is higher in PCOS, and therefore PSA can be considered a suitable marker of female hyperandrogenism.

Inter and intra-individual variability of sperm morphology after selection with three different techniques : layering, swimup from pellet and percoll

Sperm morphology has been suggested to be one of the most reliable factor in predicting male fertility potential both in spontaneous cycles and in assisted reproduction. In this work the morphology of spermatozoa selected with three different techniques (layering, swimup from pellet and mini-percoll) has been assessed and compared in 20 infertile patients. All the techniques allowed the recovery of sperm populations of a better quality than in basal samples, with a higher percentage of normal forms (p<0.001). No significant differences were observed among the three different techniques in selecting sperm populations. The scatter diagrams comparing pairwise differences between the methods against their means regard the percentage of normal forms selected show a great (over 20%) inter and intra-individual variability. These data demonstrate that the three techniques select different percentages of normal spermatozoa, even in the same patient. Since it is crucial to obtain the highest number of morphologically normal and motile spermatozoa and each technique may provide different results in a given patient, we suggest that at least two techniques of sperm selection be performed before assisted reproduction procedures. This combined testing could also be relevant in the prognostic evaluation of the infertile male, since it explores the different characteristics of sperm function.

Treatment of androgen excess in females: Yesterday, today and tomorrow

Hirsutism, acne and androgenic alopecia represent, in females, some of the manifestations of the clinical spectrum of hyperandrogenism. These pictures represent not only cosmetic damage, but also a source of remarkable psychological distress. Often hirsutism is regarded as presumptive evidence of a lack of femininity. The major diagnostic concern is to exclude an ovarian or adrenal androgen-secreting tumor, a congenital hyperplasia or polycystic ovary disease. Ethnic background should be taken into account together with the progression of the symptoms. Following the etiology, surgery and exogenous glucocorticoids or inhibition of gonadotropin secretion have to be carefully chosen in the management of different kinds of hyperandrogenism. Several pharmacologic agents have recently shown the ability to block the androgen receptors at target organ sites, thus allowing a specific antiandrogenic treatment. In some cases cosmetic measures could be of great value. Obesity accompanied by hyperinsulinemia can represent the main cause of ovary androgen hypersecretion; therefore a reduced body weight and muscle activity represent the basis of any treatment. Some other drugs, such as long-acting analogs of somatostatin, could be considered among possible drugs for the future. The aim of this article is to provide an appraisal of what is presently known about the regulation of hair growth, the various causes of excessive androgen secretion and the current methods to solve, safely, this important feminine clinical problem.

Description of an AGPAT2 pathologic allelic variant in a 54-year-old Caucasian woman with Berardinelli-Seip syndrome

A 54-year-old Italian female patient was admitted to our Department with the diagnosis of type 2 diabetes poorly controlled with insulin therapy. The patient was born by consanguineous parents (first degree cousins); she had acromegaloid features, diffuse lipoatrophy and muscular pseudo-hypertrophy since childhood. To confirm the clinical hypothesis of congenital generalized lipodystrophy (CGL) or Berardinelli-Seip syndrome, the sequences of AGPAT2 (encoding for 1-acyl-sn-glycerol-3-phosphate acyltransferase beta) and BSCL2 (encoding for seipin) candidate genes were analyzed. DNA analysis showed the presence of a homozygous mutation in exon 3 of the AGPAT2 gene (P112L). This is the first description of a Caucasian subject with CGL who carries the pathologic allelic variant P112L of the AGPAT2 gene.

Long-term intramuscular administration of thyrotropin-releasing hormone tartrate in patients with cerebrovascular disease: effects on the pituitary-thyroid axis.

We studied the effects of long-term (30 days) refracted daily intramuscular administration of 4 mg TRH tartrate (TRH-T) on the pituitary-thyroid axis in 20 euthyroid patients affected by cerebrovascular disease (CVD). All subjects were assayed for T4, T3, FT4, FT3, TSH and TBG plasma levels before treatment (D0), after 15 and 30 treatment days (D15, D30), and after a 15-day washout (D45). In addition, TSH response to 200 micrograms intravenous TRH was assessed at D0, D30 and D45. We observed a significant increase in T4, FT4 and FT3 levels in the face of decreased TSH concentrations. A blunted TSH response to TRH bolus persisted at D30. These data demonstrate that the down-regulation mechanism may be partially overcome in vivo when thyrotrophs are chronically exposed to pharmacological TRH-T doses and that TSH pattern is mainly due to the negative feedback of thyroid hormones, even though pituitary TSH reserves may become depleted. Furthermore, prolonged TRH-T administration does not produce hyperthyroidism in euthyroid CVD patients.

A rare association between malignant mediastinal seminoma and other malignant neoplasms

Primary malignant mediastinal seminomas (PMMS) are rare tumors accounting for 1–6% of all mediastinal tumors. PMMS mostly affect young men, arising from primordial germ cells that abnormally migrate from the ectoderm of the yolk sac to the gonadal region. They are clinically and biologically distinct from primary testicular tumors and seem to have a worse prognosis. Due to the rarity of the disease, the choice of treatment is a matter of debate. Literature data do not show any association between this kind of tumor and malignant Schwannoma or thyroid carcinoma. In this report we describe the case of a patient affected by PMMS and 12 yr later by a malignant brachial plexus Schwannoma and papillary thyroid carcinoma (PTC). Since both mediastinal seminoma and Schwannoma were treated with surgery followed by local radiotherapy, we were not able to ascertain if either PTC or Schwannoma had been induced by radiotherapy or represented a casual neoplastic association.