Sex hormone binding globulin, cortisol binding globulin, thyroxine binding globulin, ceruloplasmin: changes in treatment with two oral contraceptives low in oestrogen.

It is generally assumed that the oral contraceptives cause the carrier proteins to change. Notoriously this effect is used to evaluate indirectly their estrogenicity/gestagenicity ratio. In order to assess the residual intrinsic androgenic activity of two new 19-nor-derivative components, Desogestrel (DG) 150 micrograms and Gestodene (GD) 75 micrograms, both in association with Ethinylestradiol (EE) 30 micrograms, Sex Hormone Binding Globulin, Thyroxine Binding Globulin, Ceruloplasmin and Free Androgen Index (FAI), were studied in 40 young normally cycling healthy volunteers, matched for body mass index and age. The participants were randomly assigned to either EE-DG or EE-GD treatment. A marked significant increase in all the carrier proteins was found. Conversely, the values for FAI decreased significantly. The changes in the two groups were substantially of the same magnitude. These results are an indirect confirmation of the well-known negligible receptor binding affinity of the two progestogen in vitro, also supporting for these compounds the lack of relevant androgenic effects.

PIP: The residual androgenic activity of two new combined oral contraceptives (OCs)--30 mcg of ethinyl estradiol in combination with either 150 mg of desogestrel or 75 mcg of gestodene--was investigated in 40 healthy volunteers. Measured in these volunteers were modifications in transport protein levels. These levels are known to be increased by estrogen, but this increase can be counterbalanced, to varying degrees, by gestagens. For both OCs, there was a marked percentage increase in sex hormone binding globulin (SHBG), corticosteroid binding globulin (CBG), thyroxine binding globulin (TBG), and ceruloplasmin (CP) and a similar reduction in total testosterone and the free androgen index. The modifications in SHBG, CBG, TBG, and CP are interpreted as an expression of the correlated value of the estrogenicity/gestagenicity ratio of the OCs studied and suggest that these particular formulations have greater estrogenicity. The relatively negligible biological androgenic activity of desogestrel and gestodene and their elevated affinity progesterone receptor/androgen receptor ratio reflect the high selectivity of these agents. Moreover, the lack of androgenic effects makes desogestrel and gestodene appropriate treatment agents for hyperandrogenism.

Changes in the plasma levels of proteins C and S in young women on low-dose oestrogen oral contraceptives.

The physiological importance of proteins C and S as natural anticoagulants is demonstrated by the increased risk of thromboembolic disease among subjects with hereditary deficiency of both proteins. In the present study the effects were evaluated of low-dose oestrogen oral contraceptives (OC) on the plasma levels of immunological protein S, as free (PS-f), and in reversible complex with C4b-binding protein as well as functional protein C (PC) in a homogeneous group of 20 young healthy women. The participants were randomly given either gestodene (75 micrograms) or desogestrel (150 micrograms) in combination with ethinyl oestradiol (30 micrograms). Blood samples were taken prior to the initiation of the treatment and at the end of the sixth 21-day treatment cycle. The mean concentration of both free and bound PS fell significantly, the decrease still being within the reference range. Conversely, the plasma values for PC rose to a statistically significant extent. There were no significant differences between the two OCs. Hypothetically, the changes in PS-f (active fraction) might be conducive to a procoagulant state, which the increased PC may compensate. The reverse effect of two OCs on the activity of the protein C-protein S anticoagulant system might suggest a different regulation of their synthesis.

PIP: The influence of low-dose oral contraceptives (OCs) on plasma levels of proteins C and S was investigated i 20 healthy women. These proteins, along with antithrombin III, are the most significant inhibitors of coagulation. Blood samples were collected after 6 months of treatment with an OC containing 30 mcg of ethinyl estradiol and either 150 mcg of desogestrel or 75 mcg of gestodene. A significant increase in functional protein C concentrations (from 55.70 + or - 9.84 to 117.48 + or - 21.29 in the desogestrel group and 68.80 + or - 19.11 to 135.60 + or - 28.66 in the gestodene group) was recorded between baseline and the 6-month measurement. There was a corresponding decrease in plasma concentrations of free protein S (from 98.48 + or - 9.64 to 73.96 + or - 12.07 in the desogestrel group and 104.79 + or - 31.52 to 83.14 + or - 18.28 in the gestodene group). Although these OC-induced changes were statistically significant, all values remained within the normal range. The differences between the 2 OC formulations were not significant. It is hypothesized that the changes in the active fraction of protein S recorded in OC users produce a procoagulant state and increases in protein C reflect an effort to compensate for this change. The findings that OC use increases protein C and decreases protein S values suggests that the two proteins differ in the regulation of their synthesis.

Treatment of hirsutism related to micropolycystic ovary syndrome (MPCO) with two low-dose oestrogen oral contraceptives: a comparative randomized evaluation.

In order to evaluate the clinical and endocrinological efficacy of two low-dose oral contraceptives (OC) containing 30 micrograms Ethinylestradiol (EE) and 150 micrograms Desogestrel (DG) and 75 micrograms Gestodene (GD), respectively, an open randomized study was carried out in 34 young hirsute women, matched for body mass index and age. All of them met endocrine and ultrasonic criteria for Micropolycystic Ovary Syndrome (MPCO). The participants were randomly assigned to one of two pill groups (each of 17). The serum values for Total Testosterone (TT), Free Testosterone (FT), Androstenedione (A), Dehydroepiandrosterone (DHEA), Dehydroepiandrosterone Sulphate (DHEAS), 17-Hydroxyprogesterone (17Pg), Sex Hormone Binding Globulin (SHBG), Ceruloplasmin (CP), as well as Ferriman-Gallwey Index (FGI) and Free Androgen Index (FAI) were evaluated prior to and after EE-DG and EE-GD 6 cycle treatment. A significant decrease in TT, FT, A, 17Pg, DHEA, DHEAS, FGI, FAI was observed, SHRG and CP increased significantly. There were no significant differences between the two OC. Our results seem to indicate that both OC are equipotent as far as their pharmacological profile and residual androgenic activity are concerned. Therefore, these OC may represent a highly effective and suitable alternative to the treatment of hyperandrogenism related to MPCO.

PIP: In order to evaluate the clinical and endocrinological efficacy of 2 low-dose oral contraceptives (OCs) containing 30 mcg ethinyl estradiol (EE) and 150 mcg desogestrel (DG) and 75 mcg gestodene (GD) respectively, an open randomized study was carried out on 34 young, hirsute women, matched for body mass index and age. All met endocrine and ultrasonic criteria for micropolycystic ovary syndrome (MPCO); participants were randomly assigned to 1 of 2 pill groups (n=17 each). The serum values for total testosterone (TT), free testosterone (FT), androstenedione (A), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphase (DHEAS), 17-hydroxyprogesterone (17Pg), sex hormone binding globulin (SHBG), ceruloplasmin (CP), as well as Ferriman-Gallway Index (FGI), and Free Androgen Index (FAI) were evaluated prior to and after EE-DG and EE-GD 6-cycle treatment. Significant decreases in TT, FT, A, 17PG, DHEA, DHEAS, FGI, and FAI were observed; SHBG and CP increased significantly. There were no significant differences between the 2 OCs. These results seem to indicate the both OCs are equally potent in pharmacological profile and residual androgenic activity. Therefore, these OCs may represent a highly effective and suitable alternative to the treatment of hyperandrogenism related to MPCO.

Effects of desogestrel and gestodene in low-dose oral contraceptive combinations on lipid and lipoprotein status. A randomized prospective study.

This study was designated to assess the effects of two low-dose oral contraceptives (OC) on serum lipids and lipoproteins and to compare, at same oestrogen dose (30 micrograms), the effects of desogestrel (DG) with those of a new progestin, gestodene (GD). Fifty-four young women, matched for Quetelet's Index, age, diet, alcohol consumption, smoking and exercise habits, were randomly assigned to one of two regimens. Serum high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total triglycerides (T) and cholesterol (C), apolipoprotein A-1 (Apo A) and apolipoprotein B (Apo B) were measured prior to the OC commencement and after 6-cycle treatment. Sex hormone binding globulin (SHRG) and ceruloplasmin (CP) were determined as well. LDL-C, Apo A, C, T, increased significantly from baseline values, being still the increase within the reference range. Apo B changed proportional to the LDL-C increase. A rise in HDL-C occurred but it was statistically significant in the EE-DG group only. This result would suggest that the EE-DG combination is more estrogen-dominant that the EE-GD combination. However, this hypothesis was not consistent with the increase to the similar extent for SHBG and CP, which reflect the estrogenicity/gestagenicity of the two OCs. The disproportion of change between HDL-C and Apo A in only EE-GD group might reflect some compositional change in HDL particle. There were no significant differences between the two formulations for the parameters investigated.

PIP: This study was designed to assess the effects of 2 low-dose oral contraceptives (OCs) on serum lipids and lipoproteins and to compare, at the same 30 mcg estrogen dose, the effects of desogestrel (DG) with those of a new progestin, gestodene (GD). 54 young women, matched for Quetelet's Index, age, diet, alcohol consumption, smoking, and exercise habits, were randomly assigned to 1 of 2 regimens. Serum high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL), cholesterol, total triglycerides (T), and cholesterol (C), apolipoprotein A-1 (Apo A), and Apo B were measured prior to the OC commencement and after 6 cycles of treatment. Sex hormone binding globulin (SHBG) and ceruloplasmin (CP) were determined as well. LDL-C, Apo A, C, and T increased significantly from baseline values, still remaining within the reference range. Apo B changed proportionally to the LDL-C increase. A rise in HDL-C occurred but it was statistically significant in the EE-DG group only. This result would suggest that the EE-DG combination is more estrogen dominant than the EE-GD combination; however this was not consistent with the increase to a similar extent of SHBG and CP, which reflect the estrogenicity/gestagenicity of the 2 OCs. The disproportionate change between HDL-C and Apo A in only the EE-GD group might reflect some compositional change in HDL particles. There were no significant differences between the 2 formulations for the parameters investigated.

[Solitary and multiple thyroid nodular pathology (results of 1,300 surgical interventions)]. / Patologia nodulare tiroidea solitaria e multipla (risultati di 1.300 interventi chirurgici).

To evaluate the results of single and multinodular thyropathies surgical treatment, 1.300 cases operated on from january 1974 to december 1987 were reviewed. 842 patients (64.7%) were female; the average age was 41 +/- 2.4 year. Thyroid pathology was represented by solitary nodule in 643 cases (49.4%); multinodular goitre in 559 cases (43.0%) (377 euthyroid, with multinodular lesions extended to the entire gland; 182, hyperthyroid); retrosternal goitre in 78 cases (5.9%); recurrent goitre in 20 cases (1.5%). The patients underwent to: total thyroidectomy (525 cases); subtotal thyroidectomy (132 cases); total lobectomy (322 cases); subtotal lobectomy (321 cases). Post-operative follow-up (clinical exam; T3, T4, TSH, calcemia and phosphatemia) was performed at 3, 6, 12, 18 and 24 months after surgery). The overall mortality was 0.13 percent (two deaths, respectively after total = 0.1% and subtotal thyroidectomy = 0.7%). Immediate postoperative complications were: recurrent palsy (9 cases: 0.6%; acute respiratory failure with temporary tracheostomy (10 cases: 0.7%); hypoparathyroidism (3 cases: 0.2%). Late sequelae (1-3 year) were: recurrent nerve palsy in 7 patients (0.5%); hypoparathyroidism in one case (0.07%). 46 patients (34.8%) which underwent subtotal thyroidectomy were hypothyroid to T3, T4, TSH tests (1 year). Such sub-clinic pathology required levo-thyroxin treatment. New concepts on the pathogenesis of multinodular goitre (growth autonomy of goitre human tissue; the lack of levo-thyroxin therapy to prevent relapses after subtotal thyroidectomy) and the results drawed from the revision of this series seems confirm the indication to lobectomy for solitary "cold" nodules and thyroidectomy for treatment of normo and hyperthyroid multinodular goitre.

Effectiveness of short term canrenone treatment in idiopathic hirsutism.

In order to verify the anti-androgenic effects of canrenone, the major metabolite of spironolactone, 9 normally cycling women with post-puberal hirsutism, were orally administered the drug (200 mg per day for three months). In all patients, the clinical score, according to the method of Ferriman and Gallwey (F.G.I.: Ferriman-Gallwey Index), as well as endocrine function tests, including total and free testosterone, sex hormone binding globulin, dehydroepiandrosterone sulphate, 17-OH-progesterone, basal and ACTH stimulated cortisol, were evaluated prior to and after canrenone treatment. A significant reduction in hair growth (F.G.I. = 18 +/- 2 vs 23 +/- 3, p less than 0.001), and also a significant decrease, with regard to endocrine parameters, of total testosterone (0.5 +/- 0.1 vs 0.9 +/- 0.3 p less than 0.01), free testosterone (2.7 +/- 0.7 vs 4.7 +/- 1.7, p less than 0.005), dehydroepiandrosterone sulphate (228 +/- 38 vs 314 +/- 81, p less than 0.02), and sex hormone binding globulin (62.5% of basal values, p less than 0.001), were observed. Serum levels of 17-OH-progesterone, and basal and ACTH stimulated cortisol were not significantly different from pretreatment values. It is concluded that the biochemical and clinical parameter improvement, along with a well-preserved cortisol secretion (unchanged levels of 17-OH-progesterone), suggest that canrenone may represent an effective therapy for idiopathic post-puberal hirsutism.

Short-term treatment of hirsutism related to micropolycystic ovary syndrome with a combination type oral contraceptive containing desogestrel.

The antiandrogen effects of an oral contraceptive containing 0.03 mg. Ethinyl Oestradiol and 0.15 mg. Desogestrel have been evaluated in 17 non-obese hirsute women, with normal serum LH and FSH values and their ratio, and evidence for Micropolycystic Ovary Syndrome (MPCO) on ultrasound examination. At the completion of 5 cycles (21 days) of treatment, a statistically significant decrease in serum Total Testosterone, Free Testosterone, Androstenedione levels was observed. Similarly, serum values for Dehydroepiandrosterone Sulphate and 17-OH-Progesterone showed a marked fall. The Sex Hormone Binding Globulin (SHBG) values rose about four-fold, so that the Free Androgen Index was suppressed. The clinical score, evaluated according to the method of Ferriman and Gallwey, was found sharply reduced. Therefore, the well defined improvement of biochemical and clinical parameters, along with the absence of discernible side effects, are undoubtedly confirming the effectiveness of the treatment in hyperandrogenism of women with MPCO.

"Etiological characterization of hirsutism by means of a chemometric technique: the linear discriminant analysis".

This preliminary study concerns the evaluation of a chemometric technique, the so called Linear Discriminant Analysis (LDA) for an adequate nosological characterization of the more common forms of hirsutism: i.e., the Micropolycystic Ovary Syndrome (MPCO) and the Idiopathic Hirsutism (I.H.). The obtained data and, particularly, the evidence of statistically significant values of the Linear Discriminant Function (mean = 12.7; p less than 0.02), clearly show the effectiveness of LDA as a practical and suitable method for a more proper detection and classification of MPCO and I.H.

Abnormal daily periodicity of serum thyrotropin (TSH) and evidence for defective TSH suppression in a case of non-neoplastic syndrome of inappropriate TSH secretion.

A non-neoplastic syndrome of inappropriate secretion of TSH (ITSHS) was diagnosed in a hemithyroidectomized and clinically euthyroid 44-yr-old man, who also exhibited limping (Perthes' disease), genu valgum, pes supinatus and lateral nystagmus. Computed tomography demonstrated an enlarged sella turcica due to empty sella. Baseline serum T3, T4, free T3, free T4 and TSH fluctuated between 179 and 274 ng/dl, 6.0 and 13.2 micrograms/dl, 4.2 and 6.0 pg/ml, 7.6 and 15.3 pg/ml, and 4.3 and 33.0 microU/ml, respectively. Serum alpha-TSH subunit was repeatedly normal (0.36-0.69 ng/ml) over the follow-up period (greater than 3 yr). No changes in serum liver enzymes and lipids were observed after thyroid hormone administration, whereas red blood cell glucose-6-phosphate dehydrogenase (G-6-PD) and urinary OH-proline were slightly enhanced during 120 micrograms/day L-T3 regimen. This also resulted in an inappropriately normal glucagon-stimulated cAMP levels. Tachycardia was experienced only during L-T3 and very high L-T4 dose treatments. Therefore, the patient showed some evidence for thyroid hormone peripheral refractoriness. Patient's TSH was physiologically responsive to agents (thyrotropin releasing hormone, methimazole, the dopamine antagonists domperidone and sulpiride) known to elicit its release into circulation, while it responded paradoxically to those which normally inhibit TSH secretion. In fact, the infusion of somatostatin (320 micrograms/h) or dopamine (4 micrograms/Kg/min), and the oral administration of bromocriptine or nomifensine (two dopamine agonists) or corticosteroids (dexamethasone) provoked an unexpected elevation of both unstimulated and TRH-stimulated TSH levels.(ABSTRACT TRUNCATED AT 250 WORDS)

[Changes in the levels of reverse triiodothyronine (rT3) during and after surgery of the thyroid gland]. / Variazioni dei livelli di reverse-T3 (rT3) nel corso e dopo interventi chirurgici sulla tiroide.

The thyroid activity of twenty euthyroid patients, with single or multiple "cold" nodules was investigated, with determination of seric T3, T4, reverse-T3 (rT3) and TSH. The blood-drags were performed respectively, during (with seric samples from the inferior thyroid vein ipsilateral to the affected lobe) and after (1, 3 and 7 days) surgery. The results of this study--and particularly the significative decrease of T3 and the rapid rT3 increase, either during or after operation - suggests a condition similar to the described "Low T3 syndrome", as expression of both the stress determined by surgery and the correlated thyroid metabolic "adaptation". The clinical and biochemical euthyroidism, expressed by normal levels of TSH in all the samples, confirm the persistence of normal feed-back mechanism by the diencephalon-hypophysis-thyroid axis, even in stress conditions.

[Cytologic aspiration biopsy in the diagnosis and therapy of solitary cystic nodular thyropathies]. / La cito-biopsia aspirativa nella diagnosi e nella terapia delle tireopatie nodulari cistiche solitarie.

Between January and December 1983, 36 patients with single and benign cystic thyroid nodules underwent fine needle aspiration. They received, after fine needle aspiration, medical treatment (antiinflammatory drugs and L-T4). Clinical and ultrasonographic follow-up was performed either 6 and 18 months after FNA, to evaluate the lesion evolution. The six-month follow-up demonstrated no ultrasonographic signs of cystic lesion in 11 cases (30.6%); a decreased volume in 21 (58.3%) and four recurrences (11.1%), which underwent surgical treatment (lobectomy). In 21 patients with persistent lesions at 18 month follow-up, a cystic reduction in a 79.9% rate was documented. These data suggests the diagnostic importance of FNA and the safety of this method not only to surgical selection of patients, but also to the treatment of benign thyroid cysts.

[Functional evaluation of cystic thyroid nodules]. / Valutazione funzionale dei noduli tiroidei cistici.

7 patients (age between 22 and 52 years, mean 38.2 +/- 10.6 SD) with cystic nodules have been subjected to the same diagnostic screening (scintiscanning and echography, needle aspiration); in every subject hormonal pattern has been studied at the cyst and periphery level. The Authors found very high TG levels in the cyst's fluid, perhaps due to an increased sensitiviness to the thyrotropic hormone, and an rT3/T4 increased at periphery level, probably because an enhancement of mechanisms connected to the reuptake of iodine. These reports outline the great importance in the induction and development of cystic nodules of changes related to the enzymatic steps of iodination and coupling.

[Intraoperative functional study of unilateral cold thyroid nodules]. / Studio funzionale intraoperatorio dei noduli tiroidei freddi unilaterali.

The authors studied 7 patients (age between 22 and 52 years, mean 40.2 +/- 6.55 S.D.) with single or multiple solid nodules, localized in the same thyroid lobe. All subjects performed scintiscanning and echography for evaluating the nature of nodules. During the thyroidectomy the hormonal pattern has been studied in the venous blood of both lobes (inferior thyroid and jugular veins, homo and heterolateral). The authors found a significant decrease of T3 and T4 values with increased T3/T4 ratio at the nodular level. This report could be related to an hypothetical alteration of iodination mechanisms, maybe due to an intrinsic defect of oxidative mitochondrial systems.