Ectopic ACTH syndrome caused by pheochromocytoma: computed tomography-guided percutaneous ethanol injection as an alternative treatment.

Ectopic ACTH secretion represents 8-18% of the cases of endogenous hypercortisolism. Pheochromocytomas correspond to 2-25% of the cases and surgery is the indicated treatment. We describe a case of ACTH-secreting pheochromocytoma treated with percutaneous ethanol injection (PEI) guided by computed tomography (CT). A 71-yr-old man presented with diabetes, severe hypokalemia, weight loss, muscle weakness, and hypertension. Hormonal evaluation revealed elevated levels of urinary cortisol, ACTH, catecholamines, and urinary metanephrines. There was no cortisol or ACTH response to desmopressin stimulation test. Magnetic resonance revealed bilateral adrenal nodules, larger on the left side. The suspected diagnosis was ectopic ACTH syndrome caused by pheochromocytoma. Ketoconazole treatment resulted in reduction of urinary cortisol levels but was followed by severe cholestasis and hepatic dysfunction, preventing surgery; it was substituted by octreotide with reduction of ACTH and cortisol levels, but without improvement of cholestasis. The patient presented cachexia and developed multiple pulmonary abscesses that also prevented surgical treatment, thus he was treated with percutaneous ethanol injection guided by CT of the left adrenal tumor. During the procedure, the patient had an increase in blood pressure controlled by the infusion of sodium nitroprusside followed by hypotension that required infusion of dopamine and volume expansion. Afterwards, he presented hormonal normalization, normal catecholamines levels, and clinical improvement. Histological tissue analysis confirmed pheochromocytoma. We concluded that CT-guided PEI represents an efficient alternative therapy to ectopic ACTH-secreting pheochromocytomas in patients without clinical conditions for surgery.

Height and bone mineral density in androgen insensitivity syndrome with mutations in the androgen receptor gene.

INTRODUCTION AND HYPOTHESIS: Androgen insensitivity syndrome (AIS) constitutes a natural model to study effects of androgens and estrogens on growth and bone density. We evaluated height and bone density in patients with AIS with mutations in the androgen receptor (AR) gene. METHODS: A retrospective analysis was conducted of eight subjects with complete AIS (CAIS) and four with partial AIS (PAIS) submitted to gonadectomy followed by estrogen replacement, and three with PAIS who did not undergo gonadectomy. Standing height and bone mineral apparent density (BMAD) by DXA were measured and compared with male (z (m)) and female (z (f)) reference populations. The z-scores were compared with a value of zero using the one-sample t-test. RESULTS: Final heights of patients with CAIS and PAIS were intermediate between those predicted for females and males. BMAD of the lumbar spine in CAIS and PAIS after gonadectomy and estrogen replacement (z (f) = - 1.56 +/- 1.04, P = 0.006, and z (m) = - 0.75 +/- 0.89, P = 0.04) indicated vertebral bone deficit, whereas BMAD at the femoral neck was normal. No patient reported fractures. CONCLUSION: Subjects with AIS had mean final height intermediate between mean normal male and female, and decreased bone mineral density in the lumbar spine. These data suggest an important role for androgens in normal male growth and bone density not replaced by estrogens.

Pacing threshold trends and variability in modern tined leads assessed using high resolution automatic measurements: conversion of pulse width into voltage thresholds.

With the aid of an algorithm for automatic pacing threshold (T) measurement in the atrium and ventricle, downloadable into implanted Thera pacemakers (Medtronic Inc.), we studied T evolution during lead maturation, T variation during activities of daily living, and various types of beat-to-beat T variations in three tined bipolar leads: 5.6-mm2 steroid-eluting (Medtronic Inc. models 4524 atrial-J [n = 8] and 4024 ventricular [n = 8]), 1.2-mm2 steroid-eluting (Medtronic Inc. models 5534 atrial-J [n = 9] and 5034 ventricular [n = 9]), and 8-mm2 without steroid (Intermedics models 432-04 atrial-J [n = 7] and 430-10 ventricular [n = 7]). The leads were implanted in 24 consecutive patients with intact AV conduction (required by the algorithm) and followed for up to 13-25 months after implantation. Since the algorithm determined pulse width Ts at different amplitudes that, depending upon T level, could range from 0.5 to 5.0 V, we invented a methodology for conversion of pulse width Ts into voltage Ts at 0.5 ms, to pool and present T data on a universal scale. Frequent, high resolution T measurements revealed details on the lead maturation process that we divided into three stages: initial T subsiding, first wave of T peaking, and a new, quicker or slower, T rise. Although there were notable differences in duration and magnitude of T peaking on the individual basis, differences between the three lead types and between the atrium and ventricle were demonstrable. The 1.2-mm2 leads exhibited less T peaking than their predecessors 5.6-mm2 leads and excellent positional stability, whereas 8-mm2 leads demonstrated the most intensive T peaking and highest mean chronic T values. T changes during activities of daily living showed some tendencies-higher T during night and lower T during exercise--yet with a number of exceptions. The overall magnitude of daily T fluctuations was < 0.2 V in all but one lead, and 50% daily voltage safety margin would be sufficient. A 100% voltage safety margin may be inadequate for a 1-year period during the chronic phase (after 6 months of implantation). A scheme for calculation of pulse width safety margins equivalent to voltage safety margins is given. Some leads can exhibit very large beat-to-beat T variations before, during, and after T peaking, and prospective algorithms for automatic T measurement should verify T values through more than 1-2 captured beats to obviate a great underestimation of the T providing consistent capture. T dependence upon pacing rate was negligible. Consistent-capture hysteresis may, in conjunction with lead instability, be as much as 0.25 V. Therefore, it is better to use an incremental approach from below to T level during automatic T measurements.

Pacing impedance variability in tined steroid eluting leads.

The aim of the study was to investigate pacing impedance (PI) behavior in ambulatory patients. Eighteen atrial and 18 ventricular tined steroid eluting leads with 1.2-mm2 and 5.6-mm2 electrodes were implanted in 20 patients. At 9-27 months after implantation PI was measured automatically by means of additional algorithms downloaded via telemetry links into implanted Thera pulse generators. PI was determined based on the voltage drop on the output capacitor during the 5 V-1 ms pacing impulse, at the programmable sampling rates from 1 second to 30 minutes. The study examined in particular: (1) PI trends and variations associated with different breathing patterns, body postures, provocative maneuvers, bike exercise, and during 24 hours; (2) impact of pacing rate and AV-delay on PI; (3) correlation between PI variability and pacing threshold, lead configuration, absolute PI value, age, gender, disease, and cardiac chamber. The most important findings were: (1) large PI variations of up to 450 omega were observed in properly functioning leads, (2) PI variability exhibited a weak negative correlation with pacing thresholds as if electrode positional stability was not a major factor underlying PI variations, (3) unipolar and bipolar PI variations were equivalent to each other (correlation factor = 0.93) implying that PI was mostly dependent on the circumstances around the lead tip.

An algorithm for automatic measurement of stimulation thresholds: clinical performance and preliminary results.

We have developed an algorithmic method for automatic determination of stimulation thresholds in both cardiac chambers in patients with intact atrioventricular (AV) conduction. The algorithm utilizes ventricular sensing, may be used with any type of pacing leads, and may be downloaded via telemetry links into already implanted dual-chamber Thera pacemakers. Thresholds are determined with 0.5 V amplitude and 0.06 ms pulse-width resolution in unipolar, bipolar, or both lead configurations, with a programmable sampling interval from 2 minutes to 48 hours. Measured values are stored in the pacemaker memory for later retrieval and do not influence permanent output settings. The algorithm was intended to gather information on continuous behavior of stimulation thresholds, which is important in the formation of strategies for programming pacemaker outputs. Clinical performance of the algorithm was evaluated in eight patients who received bipolar tined steroid-eluting leads and were observed for a mean of 5.1 months. Patient safety was not compromised by the algorithm, except for the possibility of pacing during the physiologic refractory period. Methods for discrimination of incorrect data points were developed and incorrect values were discarded. Fine resolution threshold measurements collected during this study indicated that: (1) there were great differences in magnitude of threshold peaking in different patients; (2) the initial intensive threshold peaking was usually followed by another less intensive but longer-lasting wave of threshold peaking; (3) the pattern of tissue reaction in the atrium appeared different from that in the ventricle; and (4) threshold peaking in the bipolar lead configuration was greater than in the unipolar configuration. The algorithm proved to be useful in studying ambulatory thresholds.

Clinical use of low output settings in 1.2-mm2 steroid eluting electrodes: three years of experience.

A new generation of tined steroid-eluting leads featuring 1.2-mm2 distal electrodes (CapSure Z, Medtronic Inc., Minneapolis MN, USA) has the potential to reduce battery current drain and enhance pulse generator longevity by means of high pacing impedance and low pacing threshold. Forty patients aged 50-87 years (mean 72.4 years) were implanted with 33 ventricular (models 4033 and 5034) and 30 atrial-J (models 4533 and 5534) leads with 1.2-mm2 electrodes. Low pacing outputs, mainly in the range from 1 V/0.20 ms to 1.6 V/0.36 ms with > or = 3:1 pulse width safety margins (PWSM) applied, were instituted at 3-6 months of implantation and adjusted at subsequent follow-up controls according to changes in thresholds. Cumulative follow-up period of low outputs was 1,512 months (24 months per lead, range 9-36 months), which involved 3.43 follow-up controls per lead (range 2-5). During follow-up, pulse width thresholds (PWTs) at the used amplitudes did not change in 55.5% of the leads; PWTs increased by < or = 100% in 36.5%, by 101%-200% in 1.6%, and by > 200% in 6.3% of the leads. Changes in PWT that would apparently exceed 3:1 PWSM over a 1-year period occurred in one atrial lead where even the nominal 3.5 V/0.4-ms output would not be effective and in one ventricular lead in the aftermath of an acute myocardial infarction (300% PWT rise at 1.6 V). Based on the present observations, pacemaker dependent patients require > or = 4:1 PWSM and other patients > or = 3:1 PWSM with output pulse widths < or = 0.60 ms and annual pacemaker clinic visits. Calculated battery current drain and anticipated longevity associated with a variety of pacing outputs and impedances are provided, compared, and discussed. Correlation between acute and chronic pacing impedances and pacing thresholds was weak, implying that a systematic intraoperative pacing site optimization cannot contribute significantly to the extension of average battery longevity.

Clinical performance of steroid-eluting pacing leads with 1.2-mm2 electrodes.

To raise pacing impedance and reduce battery current drain, new tined steroid-eluting leads were developed with 1.2-mm2 hemispherical electrodes, instead of conventional 5-8 mm2. Twenty-two unipolar J-shaped atrial leads and 25 unipolar ventricular leads (models 4533 and 4033, respectively) were implanted in 33 consecutive patients and followed for a mean of 25 months (range 18-29). Handling characteristics of atrial leads were found favorable. The leads slipped easily into the right atrial appendage and were easy to position. Handling characteristics of ventricular leads were satisfying, but more efforts had to be applied to cross the tricuspid valve. Special care was taken to avoid perforation of the myocardium due to the small lead tip. Following implantation, four ventricular and one atrial lead exhibited instability of pacing thresholds that resolved spontaneously within 1-3 days of implantation. Except for this, no lead malfunctioned. The reoperation rate was zero. The mean electrogram amplitudes of 15 mV (ventricle) and 4 mV (atrium), and the mean chronic pacing threshold of 0.085 ms at 1.6 V (app. 0.43 V at 0.5 ms) were comparable with the best values seen in the literature on passive fixation leads. The rest of the electrophysiological parameters were enhanced: mean pacing impedances were 984 omega (acute) and 900 Q (chronic), mean slew rates 3.26 V/s (ventricle) and 1.75 V/s (atrium), mean acute voltage threshold at 0.5 ms was 0.25 V, mean current and energy thresholds calculated at 0.5 ms were 260 microA and 32 nJ (acute) and 478 microA and 103 nJ (chronic). The electrical characteristics of these leads provide for increased pacemaker longevity in combination with substantial safety margins for pacing and sensing.

Clinical evaluation of a thin bipolar pacing lead.

The main disadvantages of bipolar pacing leads have traditionally been related to their relative thickness and stiffness compared to unipolar leads. In a new "drawn filled tube" plus "coated wire" technology, each conductor strand is composed of MP35N tubing filled with silver core and coated with a thin ETFE polymer insulation material. This and parallel winding of single anode and cathode conductors into a single bifilar coil resulted in a bipolar lead (ThinLine, Intermedics) with a body diameter and flexibility similar to unipolar leads. The lead is tined, polyurethane, with the cathode and the anode made of iridium-oxide-coated titanium (IROX). The slotted 8-mm2 cathode tip is coated with polyethylene glycol, a blood soluble material. We present the clinical evaluation results from four pacemaker clinics, where 47 leads (23 atrial-J model 432-04 and 24 ventricular model 430-10) were implanted in 25 patients and followed for up to 2 years. The lead handling characteristics were found to be very satisfactory. Electrical parameters of the leads were measured at implant and noninvasively on postoperative days 1, 2, 21, 42, and months 3, 6, 12, and 24. Mean chronic pulse width thresholds at 2.5 V were 0.14 +/- 0.05 ms in the atrium and 0.10 +/- 0.02 ms in the ventricle, pacing impedances 443 +/- 104 omega and 520 +/- 241 omega, while median electrogram amplitudes were > or = 3.5 mV and > or = 7 mV, respectively. Pacing impedances and thresholds were found to be slightly but statistically significantly higher in unipolar than in bipolar configuration--the findings are explainable by the lead construction. One of 47 leads failed 3 weeks after implant; the conductors were short circuited due to an error during the manufacturing process. We conclude that the new lead thus far has demonstrated appropriate mechanical and electrical characteristics.

Mini-tip leads: stimulation impedance trends and daily variations

In a clinical study of a unipolar tined porous steroid-eluting lead with the cathode electrode surface area of only 1.2 mm2 (CapSure tm Z models 4533 and 4033, medtronic Inc), a total of 19 leads, ten atrial and nine ventricular, were implanted in 12 patients. Pulse generators capable of automatic measurement and recording of pacing impedance over a long-term period (Thera, Medtronic Inc) were used. The mean impedance during the first six months after implant, with all the leads included, was consientlly 900. Observed daily variations were also consistent, and the six-month average ranged rom 50 to 280 in different leads. The variations were not considered to indicate lead instability.