Italian Guidelines for the Management of Sporadic Primary Hyperparathyroidism.

AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of sporadic primary hyperparathyroidism (PHPT) in adults. PHPT management in pregnancy was not considered. METHODS: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) and Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro (SIOMMMS) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for the clinical practice recommendations. RESULTS: The present GL provides recommendations about the roles of pharmacological and surgical treatment for the clinical management of sporadic PHPT. Parathyroidectomy is recommended in comparison to surveillance or pharmacologic treatment in any adult (outside of pregnancy) or elderly subject diagnosed with sporadic PHPT who is symptomatic or meets any of the following criteria: • Serum calcium levels >1 mg/dL above the upper limit of normal range. • Urinary calcium levels >4 mg/kg/day. • Osteoporosis disclosed by DXA examination and/or any fragility fracture. • Renal function impairment (eGFR <60 mL/min). • Clinic or silent nephrolithiasis. • Age ≤50 years. Monitoring and treatment of any comorbidity or complication of PHPT at bone, kidney, or cardiovascular level are suggested for patients who do not meet the criteria for surgery or are not operated on for any reason. Sixteen indications for good clinical practice are provided in addition to the recommendations. CONCLUSION: The present GL is directed to endocrinologists and surgeons - working in hospitals, territorial services or private practice - and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.

A pharmacoeconomic analysis from Italian guidelines for the management of prolactinomas.

Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma. Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies. Methods: The researchers conducted a systematic literature review for each research question on scientific databases and surveyed a panel of experts for each therapeutic procedure's specific drivers that contributed to its total cost. Results: The average cost of the first year of treatment was €2,558.91 and €3,287.40 for subjects with microprolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after initial treatment were €798.13 and €1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of €3,201.15 compared to bromocriptine, based on a willingness-to-pay of €40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic surgery was more cost-effective than cabergoline, with an ICER of €44,846.64. Considering a willingness-to-pay of €40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that. Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources.

Italian Guidelines for the Management of Prolactinomas.

INTRODUCTION: This guideline (GL) is aimed at providing a reference for the management of prolactin (PRL)-secreting pituitary adenoma in adults. However, pregnancy is not considered. METHODS: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinologi (AME) has identified potentially relevant outcomes, which have then been rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" have been considered in the systematic review of evidence and only those classified as "critical" have been considered in the formulation of recommendations. RESULTS: The present GL provides recommendations regarding the role of pharmacological and neurosurgical treatment in the management of prolactinomas. We recommend cabergoline (Cab) vs. bromocriptine (Br) as the firstchoice pharmacological treatment to be employed at the minimal effective dose capable of achieving the regression of the clinical picture. We suggest that medication and surgery are offered as suitable alternative first-line treatments to patients with non-invasive PRL-secreting adenoma, regardless of size. We suggest Br as an alternative drug in patients who are intolerant to Cab and are not candidates for surgery. We recommend pituitary tumor resection in patients 1) without any significant neuro-ophthalmologic improvement within two weeks from the start of Cab, 2) who are resistant or do not tolerate Cab or other dopamine-agonist drugs (DA), 3) who escape from previous efficacy of DA, and 4) who are unwilling to undergo a chronic DA treatment. We recommend that patients with progressive disease notwithstanding previous tumor resection and ongoing DA should be managed by a multidisciplinary team with specific expertise in pituitary diseases using a multimodal approach that includes repeated surgery, radiotherapy, DA, and possibly, the use of temozolomide. CONCLUSION: The present GL is directed to endocrinologists, neurosurgeons, and gynecologists working in hospitals, in territorial services or private practice, and to general practitioners and patients.

Analysis of Signal Processing Methods to Reject the DC Offset Contribution of Static Reflectors in FMCW Radar-Based Vital Signs Monitoring.

Frequency-modulated continuous wave (FMCW) radars are currently being investigated for remote vital signs monitoring (measure of respiration and heart rates) as an innovative wireless solution for healthcare and ambient assisted living. However, static reflectors (furniture, objects, stationary body parts, etc.) within the range or range angular bin where the subject is present contribute in the Doppler signal to a direct current (DC) offset. The latter is added to the person's information, containing also a useful DC component, causing signal distortion and hence reducing the accuracy in measuring the vital sign parameters. Removing the sole contribution of the unwanted DC offset is fundamental to perform proper phase demodulation, so that accurate vital signs monitoring can be achieved. In this work, we analyzed different DC offset calibration methods to determine which one achieves the highest accuracy in measuring the physiological parameters as the transmitting frequency varies. More precisely, by using two FMCW radars, operating below 10 GHz and at millimeter wave (mmWave), we applied four DC offset calibration methods to the baseband radar signals originated by the cardiopulmonary activities. We experimentally determined the accuracy of the methods by measuring the respiration and the heart rates of different subjects in an office setting. It was found that the linear demodulation outperforms the other methods if operating below 10 GHz while the geometric fitting provides the best results at mmWave.

Modified FMCW Scheme for Improved Ultrasonic Positioning and Ranging of Unmanned Ground Vehicles at Distances < 50 mm

Unmanned ground vehicles (UGVs) find extensive use in various applications, including that within industrial environments. Efforts have been made to develop cheap, portable, and light-ranging/positioning systems to accurately locate their absolute/relative position and to automatically avoid potential obstacles and/or collisions with other drones. To this aim, a promising solution is the use of ultrasonic systems, which can be set up on UGVs and can potentially output a precise reconstruction of the drone's surroundings. In this framework, a so-called frequency-modulated continuous wave (FMCW) scheme is widely employed as a distance estimator. However, this technique suffers from low repeatability and accuracy at ranges of less than 50 mm when used in combination with low-resource hardware and commercial narrowband transducers, which is a distance range of the utmost importance to avoid potential collisions and/or imaging UGV surroundings. We hereby propose a modified FMCW-based scheme using an ad hoc time-shift of the reference signal. This was shown to improve performance at ranges below 50 mm while leaving the signal unaltered at greater distances. The capabilities of the modified FMCW were evaluated numerically and experimentally. A dramatic enhancement in performance was found for the proposed FMCW with respect to its standard counterpart, which is very close to that of the correlation approach. This work paves the way for the future use of FMCWs in applications requiring high precision.

Optimised polymer trapped-air lenses for ultrasound focusing in water exploiting Fabry-Pérot resonance.

The concept of employing air volumes trapped inside polymer shells to make a lens for ultrasound focusing in water is investigated. The proposed lenses use evenly-spaced concentric rings, each having an air-filled polymer shell construction, defining concentric water-filled channels. Numerical simulations and experiments have shown that a plane wave can be focused, and that the amplification can be boosted by Fabry-Pérot resonances within the water channels with an appropriate choice of the lens thickness. The effect of the polymer shell thickness and the depth of the channels is discussed, as these factors can affect the geometry and hence the frequency of operation. The result was a lens with a Full Width at Half Maximum value of 0.65 of a wavelength at the focus. Results obtained on a metal-based counterpart are also shown for comparison. An advantage of this polymeric design is that it is easily constructed via additive manufacturing. This study shows that trapped-air lenses made of polymer are suitable for ultrasound focusing in water near 500 kHz.

IR Reflectography, Pulse-Compression Thermography, MA-XRF, and Radiography: A Full-Thickness Study of a 16th-Century Panel Painting Copy of Raphael.

The potential of any multi-analytical and non-invasive approach to the study of cultural heritage, both for conservation and scientific investigation purposes, is gaining increasing interest, and it was tested in this paper, focusing on the panel painting Madonna della Tenda (Musei Reali, Turin), identified as a 16th-century copy of the painting by Raffaello Sanzio. As a part of a broader diagnostic campaign carried out at the Centro Conservazione e Restauro, La Venaria Reale in Turin, Italy, the potential of the combination of X-ray radiography, pulse-compression thermography, macro X-ray fluorescence, and IR reflectography was tested to investigate the wooden support and all the preparatory phases for the realization of the painting. The results of the optical microscopy and SEM/EDS analyses on a multi-layered micro-sample were used for a precise comparison, integration, and/or confirmation of what was suggested by the non-invasive techniques. Particularly, the radiographic and thermographic techniques allowed for an in-depth study of a hole, interestingly present on the panel's back surface, detecting the trajectory of the wood grain and confirming the presence of an old wood knot, as well as of a tau-shaped element-potentially a cracked and unfilled area of the wooden support-near the hollow. The combination of radiography, macro X-ray fluorescence, Near Infrared (NIR), and Short Wave Infrared (SWIR) reflectography allowed for an inspection of the ground layer, imprimitura, engravings, and underdrawing, not only revealing interesting technical-executive aspects of the artwork realization, but also highlighting the advantages of an integrated reading of data obtained from the different analytical techniques.

Holey-structured tungsten metamaterials for broadband ultrasonic sub-wavelength imaging in water.

Metamaterials exhibiting Fabry-Pérot resonances are shown to achieve ultrasonic imaging of a sub-wavelength aperture in water immersion across a broad bandwidth. Holey-structured metamaterials of different thickness were additively manufactured using a tungsten substrate and selective laser melting, tungsten being chosen so as to create a significant acoustic impedance mismatch with water. Both broadband metamaterial behavior and sub-wavelength imaging in water are demonstrated experimentally and validated with finite element simulations over the 200-300 kHz range.

Trapped air metamaterial concept for ultrasonic sub-wavelength imaging in water.

Acoustic metamaterials constructed from conventional base materials can exhibit exotic phenomena not commonly found in nature, achieved by combining geometrical and resonance effects. However, the use of polymer-based metamaterials that could operate in water is difficult, due to the low acoustic impedance mismatch between water and polymers. Here we introduce the concept of "trapped air" metamaterial, fabricated via vat photopolymerization, which makes ultrasonic sub-wavelength imaging in water using polymeric metamaterials highly effective. This concept is demonstrated for a holey-structured acoustic metamaterial in water at 200-300 kHz, via both finite element modelling and experimental measurements, but it can be extended to other types of metamaterials. The new approach, which outperforms the usual designs of these structures, indicates a way forward for exploiting additive-manufacturing for realising polymer-based acoustic metamaterials in water at ultrasonic frequencies.

Ultrasonic Propagation in Highly Attenuating Insulation Materials.

Experiments have been performed to demonstrate that ultrasound in the 100-400 kHz frequency range can be used to propagate signals through various types of industrial insulation. This is despite the fact that they are highly attenuating to ultrasonic signals due to scattering and viscoelastic effects. The experiments used a combination of piezocomposite transducers and pulse compression processing. This combination allowed signal-to-noise levels to be enhanced so that signals reflected from the surface of an insulated and cladded steel pipe could be obtained.

Looking Through Paintings by Combining Hyper-Spectral Imaging and Pulse-Compression Thermography.

The use of different spectral bands in the inspection of artworks is highly recommended to identify the maximum number of defects/anomalies (i.e., the targets), whose presence ought to be known before any possible restoration action. Although an artwork cannot be considered as a composite material in which the zero-defect theory is usually followed by scientists, it is possible to state that the preservation of a multi-layered structure fabricated by the artist's hands is based on a methodological analysis, where the use of non-destructive testing methods is highly desirable. In this paper, the infrared thermography and hyperspectral imaging methods were applied to identify both fabricated and non-fabricated targets in a canvas painting mocking up the famous character "Venus" by Botticelli. The pulse-compression thermography technique was used to retrieve info about the inner structure of the sample and low power light-emitting diode (LED) chips, whose emission was modulated via a pseudo-noise sequence, were exploited as the heat source for minimizing the heat radiated on the sample surface. Hyper-spectral imaging was employed to detect surface and subsurface features such as pentimenti and facial contours. The results demonstrate how the application of statistical algorithms (i.e., principal component and independent component analyses) maximized the number of targets retrieved during the post-acquisition steps for both the employed techniques. Finally, the best results obtained by both techniques and post-processing methods were fused together, resulting in a clear targets map, in which both the surface, subsurface and deeper information are all shown at a glance.

Delamination Detection in Polymeric Ablative Materials Using Pulse-Compression Thermography and Air-Coupled Ultrasound.

Ablative materials are used extensively in the aerospace industry for protection against high thermal stresses and temperatures, an example being glass/silicone composites. The extreme conditions faced and the cost-risk related to the production/operating stage of such high-tech materials indicate the importance of detecting any anomaly or defect arising from the manufacturing process. In this paper, two different non-destructive testing techniques, namely active thermography and ultrasonic testing, have been used to detect a delamination in a glass/silicone composite. It is shown that a frequency modulated chirp signal and pulse-compression can successfully be used in active thermography for detecting such a delamination. Moreover, the same type of input signal and post-processing can be used to generate an image using air-coupled ultrasound, and an interesting comparison between the two can be made to further characterise the defect.

Holter monitoring to detect silent atrial fibrillation in high-risk subjects: the Perugia General Practitioner Study.

Atrial fibrillation (AF) is diagnosed for the first time in about 5 % of patients admitted for acute ischemic stroke. Advanced aged and arterial hypertension are risk factors for AF. We evaluated the prevalence of silent AF in subjects with advanced age and systemic arterial hypertension. Subjects of both gender, aged 65 years or more with systemic arterial hypertension were randomly identified from the patient lists of the participating general practitioners in the Perugia area, in Italy. Study subjects underwent baseline 12-lead ECG and, if this did not show AF, 48-h Holter monitoring was performed. AF was known and confirmed by 12-lead ECG in 4 out of the 308 evaluated subjects (1.3 %). Baseline 12-lead ECG showed no cases of silent AF. Holter monitoring was performed in 300 subjects, mean age 70 ± 4. Twenty-six recordings were not evaluable for the presence of artifacts; therefore, 274 subjects were included in the analysis. Holter monitoring showed AF in 27 out of 274 subjects (10 %; 95 % confidence interval 6.4-13.5 %); AF was longer than 30 s in four of the subjects. In 56 additional subjects, Holter monitoring revealed excessive supraventricular ectopic activity (20 %; 95 % confidence interval 15.3-24.7 %). Holter monitoring was able to detect silent AF in about 10 % of subjects aged 65 or above with systemic arterial hypertension. The risk of stroke associated with screened silent AF should be carefully evaluated.

Coded waveforms for optimised air-coupled ultrasonic nondestructive evaluation.

This paper investigates various types of coded waveforms that could be used for air-coupled ultrasound, using a pulse compression approach to signal processing. These are needed because of the low signal-to-noise ratios that are found in many air-coupled ultrasonic nondestructive evaluation measurements, due to the large acoustic mismatch between air and many solid materials. The various waveforms, including both swept-frequency signals and those with binary modulation, are described, and their performance in the presence of noise is compared. It is shown that the optimum choice of modulation signal depends on the bandwidth available and the type of measurement being made.

Mapping of human autoantibody epitopes on aromatic L-amino acid decarboxylase.

CONTEXT: Aromatic l-amino acid decarboxylase (AADC) is target of autoantibodies in autoimmune polyendocrine syndrome I (APS I), especially in patients with autoimmune hepatitis. Little information is currently available on AADC autoantibody epitopes and on the interrelation between autoantibody-mediated inhibition of enzymatic activity and epitope specificity. DESIGN: We tested the immunoreactivity of full-length porcine AADC and of eight fragments of the enzyme with human serum from 18 patients with APS I, 199 with non-APS I autoimmune Addison's disease, 124 with type 1 diabetes mellitus, 36 with Graves' disease, and 141 healthy control subjects, and we evaluated the autoantibody-mediated enzymatic inhibition. RESULTS: AADC antibodies (Ab) were detected in 12 of 18 (67%) APS I patients and in six of 199 (3%) autoimmune Addison's disease patients. Four patients with autoimmune hepatitis were all positive for AADCAb. None of the 141 healthy control subjects, 82 patients with nonautoimmune adrenal insufficiency, 124 with type 1 diabetes mellitus, and 36 with Graves' disease were found positive. Two epitope regions, corresponding to amino acids 274-299 (E1) and 380-471 (E2) were identified. Localization of E1 was confirmed by displacement studies with synthetic peptides corresponding to peptides of porcine AADC. All 12 AADCAb-positive APS I sera reacted with E1, and seven of 12 (58%) reacted also with E2. E2-specific, but not E1-specific, autoantibodies were associated with a significant inhibition of in vitro AADC enzymatic activity. CONCLUSIONS: We mapped the human AADCAb epitopes to the middle and COOH-terminal regions of the enzyme. Autoantibodies to the COOH-terminal region induce a significant inhibition of enzymatic activity.

Elevated serum interferon-gamma-inducible chemokine-10/CXC chemokine ligand-10 in autoimmune primary adrenal insufficiency and in vitro expression in human adrenal cells primary cultures after stimulation with proinflammatory cytokines.

Chemokines are a large family of cytokines involved in the pathogenesis of inflammatory and autoimmune diseases. Among CXC chemokines, CXC chemokine ligand 10 (CXCL10) has been identified to play an important role in several endocrinological autoimmune diseases, such as Hashimoto's thyroiditis, Graves' disease, and type 1 diabetes mellitus. Although the mechanisms leading to glandular autoimmune process may be at least in part shared by different endocrine organs, the role of CXCL10 in autoimmune adrenal insufficiency is unknown. The aim of this study was to evaluate the role of CXCL10 in Addison's disease (AD). Serum CXCL10 levels were assayed in 64 patients with clinically evident autoimmune AD, 20 patients with autoimmune subclinical AD, nine patients with nonautoimmune AD, and 48 healthy volunteers. Clinically evident and subclinical AD, but not nonautoimmune AD patients, showed a significant increase in serum CXCL10 levels compared with healthy subjects: 119.9 pg/ml (range, 39.8-427.6) and 124.0 pg/ml (range, 37.0-384.7) vs. 75.6 pg/ml (range, 22.4-164.0; P < 0.001 for both groups). Comparable serum CXCL10 levels were found between patients with an isolated form of AD and patients with other autoimmune conditions associated with AD, suggesting a specific influence of the adrenal autoimmune process in determining elevated CXCL10 concentrations in such patients. No relationship was found between serum CXCL10 levels and anti-21-hydroxylase or adrenal cortex autoantibody titers or between CXCL10 levels and duration of disease. The role of CXCL10 in the adrenal gland was also evaluated in vitro in human zona fasciculata cells (hZFC). CXCL10, although not basally detected in cultured hZFC, was strongly induced by interferon-gamma and synergistically increased by TNF-alpha addition. Hydrocortisone or ACTH alone had no effect on CXCL10 secretion in hZFC, but they both significantly inhibited cytokine-induced CXCL10 secretion. Taken together, these data suggest a potential role of hZFC, through the production of CXCL10, in regulating the recruitment of specific subsets of activated lymphocytes in autoimmune AD.

Italian addison network study: update of diagnostic criteria for the etiological classification of primary adrenal insufficiency.

Primary adrenal insufficiency (PAI) is clinically evident in one in 8000 individuals. A correct etiological classification is critical for correct disease management. To update the diagnostic criteria for the etiological classification of PAI, a multicentric network was established in Italy, and 222 patients with PAI were studied. Both 21-hydroxylase and adrenal cortex autoantibodies (21OHAb and ACA, respectively) were tested in two independent laboratories on coded samples and found in 65-66% and 58-61% of cases, respectively. Autoimmune polyendocrine syndrome I was diagnosed in 11 of the 222 patients. Of the remaining 211 patients, 38 (18%) had a nonautoimmune form of PAI. In 145 subjects (65%), the presence of adrenal autoantibodies, without signs of other forms of PAI, led to a diagnosis of autoimmune Addison's disease. In six cases (3%), PAI remained idiopathic. Logistic regression analysis showed a 92.2-92.7% probability of correct reclassification for the two 21OHAb assays and 84.5-85.9% for the ACA assays. We conclude that the simultaneous presence of both 21OHAb and ACA permits unambiguous diagnosis of autoimmune Addison's, whereas subjects with low antibody titers should undergo both instrumental and biochemical tests to exclude other causes of PAI. Lastly, we developed a comprehensive flowchart for the classification of PAI for use in routine clinical practice.

Dehydroepiandrosterone, 17alpha-hydroxyprogesterone and aldosterone responses to the low-dose (1 micro g) ACTH test in subjects with preclinical adrenal autoimmunity.

OBJECTIVE: The appearance of 21-hydroxylase autoantibodies (21OHAbs) identifies subjects with preclinical adrenal insufficiency. In 21OHAb-positive subjects, the adrenocortical function is best evaluated by peak cortisol (F) levels after the low-dose (1 micro g) ACTH stimulation test (LDT). No information is currently available on the correlation between F and other adrenocortical hormone responses to the LDT in subjects with an ongoing autoimmune adrenal process. In this study, we tested the hypothesis that the dehydroepiandrosterone (DHEA), 17alpha-hydroxyprogesterone (17OHP) and aldosterone (A) responses to the LDT are consensual to that of F during the preclinical phase of autoimmune adrenal insufficiency. DESIGN AND PATIENTS: We studied 12 subjects positive for 21OHAb, in the absence of clinical signs of adrenal insufficiency. On the basis of peak F levels after the LDT, and according to the lower level of normal observed in 15 healthy volunteers (510.4 nmol/l), patients were subdivided into two groups: group A, n = 6 subjects with normal F response; and group B, n = 6 subjects with impaired F response. Results were expressed as absolute delta increase (Delta) between peak and basal levels. RESULTS: DeltaF was significantly higher in group A (314.5 +/- 115.8 nmol/l) than in group B (151.7 +/- 88.2 nmol/l) (P = 0.041). DeltaDHEA and Delta17OHP were also significantly higher in group A (17.0 +/- 13.5 nmol/l and 6.1 +/- 4.4 nmol/l, respectively) than in group B (0.69 +/- 2.25 nmol/l and 1.9 +/- 1.7 nmol/l, respectively) (P = 0.002 and P = 0.041). The difference in DeltaA between the two groups did not reach statistical significance (group A 321.8 +/- 272.0 pmol/l vs. group B 157.0 +/- 154.0 pmol/l). DeltaDHEA, Delta17OHP and DeltaA tended to correlate positively with DeltaF (P = 0.039, P = 0.039 and P = 0.044, respectively), but the correlations did not reach significance after correction of the P-value. CONCLUSIONS: Our study demonstrates a high concordance between F and DHEA, 17OHP and A responses to the LDT in subjects with preclinical adrenal autoimmunity, thus strengthening the concept that the LDT is an accurate test to identify early adrenal dysfunction.

Steroid-cell autoantibodies are preferentially expressed in women with premature ovarian failure who have adrenal autoimmunity.

OBJECTIVE: To determine the prevalence of steroid-cell autoantibodies, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) antibodies, 17alpha-hydroxylase (17alpha-OH) antibodies, and P450 side-chain cleavage antibodies in premature ovarian failure. DESIGN: Cross-sectional, observational study. SETTING: Academic research hospitals. PATIENT(S): Eighty-one women with premature ovarian failure, 20 women with Addison disease not associated with premature ovarian failure, 42 women with type 1 diabetes mellitus, and 90 healthy women. MAIN OUTCOME MEASURE(S): Serum levels of steroid-cell autoantibodies, 17alpha-OH antibodies, P450 side-chain cleavage antibodies, and 3beta-HSD antibodies. RESULT(S): Steroid-cell autoantibodies were present in none of 57 women with isolated premature ovarian failure or premature ovarian failure plus nonadrenal autoimmune disease and in 21 of 24 (87%) women with Addison disease-related premature ovarian failure. 17alpha-Hydroxylase antibodies and P450 side-chain cleavage antibodies were significantly more frequent in women positive for adrenal autoantibodies than in those negative for adrenal autoantibodies (50% vs. 0% and 71% vs. 2%, respectively). The presence of 17alpha-OH antibodies or P450 side-chain cleavage antibodies was strongly associated with presence of steroid-cell autoantibodies. Two of 24 (8%) women with Addison disease-related premature ovarian failure and 1 of 57 (2%) women with isolated premature ovarian failure or premature ovarian failure plus nonadrenal autoimmune disease were positive for 3beta-HSD antibodies. None of 20 adult women with autoimmune Addison disease and none of 42 adult women with type 1 diabetes mellitus not associated with premature ovarian failure was positive for 3beta-HSD antibodies. CONCLUSION(S): Markers of steroid-cell autoimmunity are found only rarely in idiopathic premature ovarian failure not associated with Addison disease. Most women with Addison disease-related premature ovarian failure were positive for steroid-cell autoantibodies, 17alpha-OH antibodies, or P450 side-chain cleavage antibodies. 3beta-Hydroxysteroid dehydrogenase antibodies do not appear to be a major marker of steroid-cell autoimmunity.

Autoantibodies in autoimmune polyendocrine syndrome type II.

The autoimmune polyendocrine syndrome type II (APS-II) is characterized by the association of autoimmune Addison's disease with thyroid autoimmune diseases or type-1 diabetes mellitus. 21-Hydroxylase autoantibodies enable the accurate diagnosis of autoimmune Addison's disease and, in patients with other endocrine autoimmune diseases, identify subjects at high risk for clinical adrenal insufficiency. 17 alpha-Hydroxylase (17OH) and side-chain-cleavage enzyme (P450scc) are target autoantigens of steroid-cell autoantibodies, and in women with Addison's disease, 17OH autoantibodies and P450scc autoantibodies are markers of increased risk for premature ovarian failure. Thyroperoxidase autoantibodies, thyroglobulin autoantibodies, H+/K(+)-ATPase autoantibodies, and GAD65 autoantibodies are frequently detected in patients with isolated Addison's or APS-II. Screening for other organ-specific autoimmune diseases should be performed in every patient with at least one major disease component of APS-II.