Autonomic nervous system and cardiovascular risk assessment during one year of growth hormone replacement therapy in adults with growth hormone deficiency.

OBJECTIVE: This prospective study aimed to evaluate the impact of growth hormone deficiency (GHD) on cardiac autonomic tone and on cardiovascular risk and the changes after 12 months of GH replacement therapy (GHRT). GHD is associated with increased cardiovascular morbidity and mortality. This has been attributed to increased markers of cardiovascular risk and to abnormalities of both the cardiac and peripheral autonomic nervous systems. The autonomic cardiac nervous system (ACNS) can be indirectly evaluated by analysis of heart rate variability (HRV) in clinostatism and orthostatism. DESIGN: We compared 14 GHD patients at baseline and after 12 months of GHRT and 17 healthy controls. We analyzed a number of cardiovascular risk factors and we used analysis of HRV during the Tilt Test that identified high frequency (HF) and low frequency (LF), representing parasympathetic and sympathetic activity, respectively. RESULTS: Compared with the control group, in either clinostatism or in orthostatism our patients showed a significantly lower value of LF (P=0.047; P=0.004, respectively), whereas HF was significantly reduced in orthostatism (P=0.037), and indicatively in clinostatism (P=0.065). These values remained unchanged after 12 months of GHRT. No statistically significant differences were found between the LF/HF ratio in untreated and treated patients. In GHD patients, there was a significant reduction of cardiovascular risk in 12 months of replacement therapy (P=0.002). CONCLUSIONS: Our study highlights the absence of sympathovagal imbalance in GHD patients; GHRT does not change ACNS during the first year of GH treatment but it reduces the absolute cardiovascular risk in these patients.

Identification of a novel mutation in exon 1 of androgen receptor gene in an azoospermic patient with mild androgen insensitivity syndrome: case report and literature review.

OBJECTIVE: To report a case of an azoospermic subject with mild androgen insensitivity syndrome (MAIS) and review the relevant literature. DESIGN: Case report. SETTING: Academic research hospital. PATIENT(S): A 49-year-old man with undermasculinized features and a history of cryptorchidism and azoospermia. INTERVENTION(S): Hormonal evaluation and genetic testing of the androgen receptor gene (AR). MAIN OUTCOME MEASURE(S): Hormonal levels and sequence chromatogram of the proband and his mother. RESULT(S): We found total T in the normal range and high levels of gonadotropins. Karyotype was 46,XY. Genetic testing identified a novel mutation of exon 1 of AR, which resulted in an alanine to serine substitution in the transactivation domain at codon 240 (A240S). Fourteen other mutations of exon 1 of AR have been associated with MAIS to date. CONCLUSION(S): The novel mutation A240S of AR is involved in MAIS, a syndrome associated with azoospermia.

Changes in sex steroid levels in women with epilepsy on treatment: relationship with antiepileptic therapies and seizure frequency.

PURPOSE: Reproductive dysfunction in epilepsy is attributed to the seizures themselves and also to antiepileptic drugs (AEDs), which affect steroid production, binding, and metabolism. In turn, neuroactive steroids may influence neuronal excitability. A previous study in this cohort of consecutive women with epilepsy showed that patients with more frequent seizures had higher cortisol and lower dehydroepiandrosterone sulfate levels than those with rare or absent seizures. The present study was aimed at evaluating, in these same women, the possible relationship between some clinical parameters, seizure frequency, AED therapies, and sex hormone levels. METHODS: Estradiol (E2), progesterone (Pg), sex hormone-binding globulin (SHBG), and free estrogen index (FEI) were measured during the luteal phase in 113 consecutive females, 16-47 years old, with different epilepsy syndromes on enzyme-inducing AED (EIAED) and/or non-enzyme-inducing AED (NEIAED) treatments, and in 30 age-matched healthy women. Hormonal data were correlated with clinical parameters (age, epilepsy syndrome, disease onset, and duration), seizure frequency assessed on the basis of a seizure frequency score (SFS), and AED therapies. RESULTS: E2, Pg, and FEI were lower, whereas SHBG levels were higher in the epilepsy patients than in the controls. However, sex steroid and SHBG levels were not different between groups of patients categorized according to SFS. Therapies with EIAEDs accounted for changes in E2 levels and FEI. CONCLUSIONS: Despite globally decreased sex steroid levels in serum, actual hormone titers were not significantly correlated with SFS in consecutive epilepsy women; rather, these hormonal changes were explained by AED treatments, mainly when EIAED polytherapies were given.

Pemphigus vegetans Neumann type with anti-desmoglein and anti-periplakin autoantibodies.

Pemphigus vegetans is a rare variant of pemphigus vulgaris characterized by vegetating lesions in the folds and mouth and by the presence of autoantibodies against desmoglein 3. We describe two Caucasian patients with pemphigus vegetans, one of them presented antibodies to desmoglein 3 and 1 and the other one to desmoglein 3. Both patients also had circulating antibodies against a 190 kDa protein co-migrating with periplakin. Anti-periplakin reactivity is usually detected in paraneoplastic pemphigus, while it has never been reported in pemphigus vegetans. Our observation enlarges the spectrum of autoantibodies which may be associated with pemphigus vegetans. However, the pathophysiological significance of anti-periplakin reactivity in this pemphigus variant remains to be determined.

Sympathovagal imbalance in acromegalic patients.

CONTEXT: Sympathovagal imbalance is a common finding in diabetes and is considered to be a cardiovascular risk factor. No data are available on sympathovagal balance (SB) in acromegalic patients. OBJECTIVE: The objective of this study was to evaluate SB in acromegalic patients. PATIENTS: Twenty nondiabetic, nonhypopituitary, acromegalic patients (13 women and seven men; mean age +/- sem, 51.30 +/- 3.09 yr) were compared with age-matched subjects (21 normal subjects, 20 patients with type 1 diabetes mellitus, and 15 patients with type 2 diabetes mellitus). INTERVENTIONS: Autonomic tests, used to evaluate SB, were performed by power spectral analysis of heart rate variability in clinostatism (c) and orthostatism (o), using a frequency domain method. Power spectral analysis identifies peaks of power: high frequency (HF), which expresses vagal activity, and low frequency (LF), which expresses sympathetic activity. RESULTS: Acromegalic patients displayed significantly lower LFc/HFc (P = 0.002) and LFo/HFo (P < 0.001) ratios than normal subjects. HFo was significantly higher in acromegalic patients than in normal subjects (P < 0.001) and patients with type 1 diabetes mellitus (P = 0.004), but no different from that in type 2 diabetes mellitus patients (P = 0.069). In untreated acromegalic patients, the alterations found in the whole group were confirmed; no statistically significant differences were found between untreated acromegalic patients and those treated with somatostatin analogs. Similarly, the same alterations found in the whole group were evident in the controlled acromegalic patients, and no significant differences were found between controlled and uncontrolled patients. CONCLUSION: Our study evidenced that sympathovagal imbalance in acromegalic patients, due to vagal hypertone, is difficult to reverse and is not influenced by medical therapy. This could be a new cardiovascular risk factor.

Sympatho-vagal control of heart rate variability in patients treated with suppressive doses of L-thyroxine for thyroid cancer.

OBJECTIVE: This study aimed to analyze the autonomic control of heart rate variability (HRV) in subjects receiving chronic l-thyroxine (l-T4) treatment after total thyroidectomy and (131)I therapy for differentiated thyroid carcinoma. METHODS: Blood pressure (BP) and sympatho-vagal activity (evaluated by power spectral analysis (PSA) of time-domain parameters of HRV) were studied in clinostatism and after orthostatism in 24 healthy controls, and in 12 patients taking l-T4 (125-200 mug/day) to maintain serum TSH levels at <0.01 muIU/ml. The study of HRV by PSA is a non-invasive method of analyzing sympatho-vagal control of HRV by quantifying high-frequency (HF) (0.15-0.4 Hz) and low-frequency (LF) (0.04-0.15 Hz) powers. RESULTS: Patients on L-T4 treatment had undetectable TSH levels, serum free T4 (fT4) above the normal range or at the upper limit in one case, and normal free tri-iodothyronine (fT3) levels. Heart rate and R-R intervals were not different in the two groups, both in clinostatism and in ortostatism. Systolic and mean BP were higher in patients than in controls and were inversely correlated with actual serum fT4 levels. During clinostatism, thyroid patients showed significantly lower LF power (P = 0.035), LF/(LF + HF) (P = 0.008) and LF/HF (P = 0.01) than controls. When patients moved from lying to standing, there was a significantly different decrease in orthostatic LF power (P = 0.001), LF/(LF + HF) (P = 0.044) and LF/HF (P = 0.047) versus controls. CONCLUSIONS: Changes in autonomic control of HRV, characterized by decreased sympathetic activity and impaired sympatho-vagal balance with preserved vagal tone, are detectable in patients with hyperthyroxinemia due to suppressive l-T4 therapy and increased systolic and mean, but not diastolic, BP.

Seizure frequency and cortisol and dehydroepiandrosterone sulfate (DHEAS) levels in women with epilepsy receiving antiepileptic drug treatment.

PURPOSE: Hormonal changes occur in epilepsy because of seizures themselves and of antiepileptic drug (AED) effects on steroid production, binding, and metabolism. Conversely, steroids may influence neuron activity and excitability by acting as neuroactive steroids. This cross-sectional observational study aimed to evaluating cortisol and dehydroepiandrosterone sulfate (DHEAS) levels in female epilepsy patients with different disease severity, as assessed by a seizure frequency score (SFS). METHODS: Morning serum levels of cortisol and DHEAS were assayed in 113 consecutive women, aged 16 to 47 years, with varied epilepsy syndromes, receiving mono- or polytherapy with enzyme-inducing and/or noninducing antiepileptic drugs (AEDs). Hormonal data were correlated with clinical parameters (age, body mass index, epilepsy syndrome, disease onset and duration, SFS, AED therapy, and AED serum levels) and compared with those of 30 age-matched healthy women. RESULTS: In epilepsy patients, cortisol levels and cortisol-to-DHEAS ratios (C/Dr) were significantly higher, whereas DHEAS levels were significantly lower than those in controls. Patients with more frequent seizures showed higher cortisol and C/Dr values and lower DHEAS levels than did those with rarer or absent seizures during the previous 6 months. SFS mainly explained the increase of cortisol levels and C/Dr in patients with more active disease. Changes in DHEAS levels correlated with SFS and epilepsy syndrome, as well as with AED treatments and ages. CONCLUSIONS: Women with more frequent seizures had alterations of their adrenal steroids characterized by an increase of cortisol and a decrease of DHEAS levels. Such hormonal changes might be relevant in seizure control and in patient health.