The people you met in 2009

We introduced you to many amazing people through Life feature stories in 2009. Here’s a look back at a few of those stories, along with their updates.

We’d also like to take this opportunity to thank everyone who shared their stories with Echo Press readers this past year. Every story is important, and by sharing it you have touched the lives of countless others.

One day at a time

March 11

In March, we introduced you to Stephanie Anderson of Evansville. Anderson suffers from chiari malformation, a rare neurological disorder in which brain tissue protrudes into her spinal column.

At the time of the story, Anderson had gone through three brain surgeries, none of which had been successful in eliminating the severe head and neck pain caused by the disorder.

After the story ran, Anderson worked with a pain physician and had a series of steroid shots. The steroids helped but because of the larger doses required to control the pain, she acquired Cushing’s syndrome, a reaction to the drug that caused her to gain 40 pounds. She has not been able to lose the weight because of the pain involved with exercise.

Doctors also tried implanting a neurostimulator into Anderson’s spinal column, which was not successful. Eventually, with no other methods of decreasing the pain, Anderson had to resort to narcotic pain medicines.

In the meantime, a co-worker of her husband, Mitch, informed them of a high vitamin concentrate formulated by two doctors from Minnesota. At the point where she was “open to anything that would help,” she started taking it. Since then, she has cut back on half of all the medication she is taking and hopes to cut it back even more.

“I’ve heard from many people that I am getting back to my old self,” she said. “It’s not a lot, but hopefully it will help.”

Read more http://www.echopress.com/event/article/id/71002/

Previous hypercortisolism exposure associated with Cushing’s disease increased risk for metabolic, vascular disorders

Researchers observed an increased three-year incidence of metabolic syndrome and prevalence of cardiovascular and cerebrovascular disease among growth hormone-treated patients with previous Cushing’s disease in a new study.

Researchers conducted a post hoc analysis of the observational Hypopituitary Control and Complications Study (1995-2006). The goal was to compare the prevalence and incidence of metabolic syndrome (using Adult Treatment Panel III criteria), diabetes, CV disease and cerebrovascular disease in patients with adult-onset GH deficiency who had previous Cushing’s disease (n=160) vs. previous nonfunctioning pituitary adenoma (n=879). All patients received GH, were GH-naïve at baseline and had multiple pituitary defects.

Patients with previous Cushing’s disease had a significantly greater three-year incidence of metabolic syndrome compared with previous nonfunctioning pituitary adenoma (23.4% vs. 9.2%; P=.01).

The prevalence of CVD was also greater among those with previous Cushing’s disease vs. nonfunctioning pituitary adenoma at baseline (6.3% vs. 2.2%; P<.01) and three-year follow-up (7.6% vs. 3.9%; P=.04). The researchers observed a similar trend for prevalence of cerebrovascular disease at baseline (6.4% vs. 1.8%; P=.03) and three years (10.2% vs. 2.9%; P=.01).

“These results suggest that previous exposure to hypercortisolism predisposes GH-deficient patients treated for Cushing’s disease to a greater risk of metabolic and vascular disease,” the researchers wrote. They suggested that clinicians “be especially mindful of the increased susceptibility of patients with previous Cushing’s disease to these conditions” when monitoring patients with pituitary disease.

Webb SM. J Clin Endocrinol Metab. 2009;doi: doi:10.1210/jc.2009-0806.

 

From http://www.endocrinetoday.com/view.aspx?rid=59583

(Cushing’s/pheos) Concomitant laparoscopic urological procedures: Does it contribute to morbidity?

Kamlesh Maurya, SE Sivanandam, Sudhir Sukumar, Sanjay Bhat, Ginil Kumar, Balagopal Nair
Department of Urology, Amrita Institute of Medical Sciences, Kochi - 682 041, India

Date of Submission
28-Sep-2009

Date of Acceptance
07-Nov-2009

Date of Web Publication
23-Dec-2009

Correspondence Address:
Kamlesh Maurya
Department of Urology, Amrita Institute of Medical Sciences, Kochi - 682 041
India
Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0972-9941.58500

Abstract

Aim: With advancement in minimal access surgery two laparoscopic procedures can be combined together shortening the total hospital stay, decreasing morbidity and overall reduced cost. Combining two laparoscopic procedures in a single session has been reported in general surgery. Very few articles are available in literature with regard to combined urological laparoscopic surgeries. This article retrospectively analyses the outcomes of multiple laparoscopic procedures performed in a single stage at our centre.

Materials and Methods: Patients undergoing simultaneous procedures from May 2003 to Jan 2009 were included in the study. Patients were categorised into three groups according to the primary urological organ involved, for better comparison with the control group. Diseases involving the adrenals gland were grouped in (group 1), kidney (group 2) and renal collecting system/ureter (group 3). All patients had one urological procedure for either of the above-mentioned organs combined with another surgical procedure. Similarly three control groups were chosen according to the primary urological organ involved (group 1c- unilateral laparoscopic adrenalectomy, group 2c- unilateral laparoscopic radical nephrectomy and group 3c- unilateral laparoscopic ureterolithotomy) for comparative study. The operative details, hospital stay and complications were analysed.

Results: Thirty-two patients underwent 64 laparoscopic procedures under single anaesthesia. The most common procedure in this series was laparoscopic adrenalectomy (n=34) followed by laparoscopic nephrectomy (n=13). Group 1 patients had a prolonged operative time ( P=0.012) and hospital stay ( P=0.025) when compared with group 1c. However, blood loss was comparable in both the groups. Patients in groups 2 and 3 had comparable operative times, blood loss and recovery period with respect to their controls. Intraoperatively, the end tidal carbon dioxide levels were within permissible limits. All procedures were completed using the laparoscopic approach, without any conversion.

Conclusions: Simultaneous laparoscopic procedures can be done for urological diseases in selected patients with the advantages of single anaesthesia and hospital admission without increasing the morbidity.

Keywords: Laparoscopy, simultaneous, urology

How to cite this URL:
Maurya K, Sivanandam SE, Sukumar S, Bhat S, Kumar G, Nair B. Concomitant laparoscopic urological procedures: Does it contribute to morbidity?. J Min Access Surg [serial online] 2009 [cited 2009 Dec 25];5:67-71. Available from: http://www.journalofmas.com/text.asp?2009/5/3/67/58500

Introduction

With advancement in laparoscopic surgery, combined laparoscopic procedures are now being performed for treating coexisting abdominal pathologies simultaneously. Simultaneous laparoscopic procedures for general surgical diseases have received good acceptance in world literature. ^{[1],[2],[3],[4],[5]} There have also been sporadic reports ^[6],[7],[8] of multiple laparoscopic procedures being combined for urological conditions and few short series ^[9],[10] demonstrating the feasibility of dual laparoscopic procedures in urology. The advantages of simultaneous intervention are: Reduced psychological stress, single anaesthesia, less medication, shorter hospital stay and considerable cost effectiveness. Prolonged operative time with attendant haemodynamic alterations due to the pneumoperitoneum was considered to be a limiting factor for the performance of concomitant procedures. Nevertheless, once the learning curve and the necessary expertise are achieved this problem can be overcome easily. The aim of this study is to analyse the feasibility of combining multiple laparoscopic procedures during elective urologic surgery.

Materials and Methods

We retrospectively reviewed all concomitant laparoscopic urologic procedures done at our centre during the period between May 2003 and January 2009. The inclusion criteria for the study group were (1) both the procedures should have been done by laparoscopic approach under a single anaesthesia and (2) at least one of the procedures should have been for a urological disease.

Combined laparoscopic operations in our series were done for diseases involving the upper urinary tract (kidney and renal collecting system) and the adrenal gland. These patients were broadly divided into three groups for better comparison with the control group: Group 1 consisted of patients who underwent laparoscopic adrenalectomy combined with another laparoscopic procedure. Group 2 had patients who had undergone laparoscopic nephrectomy combined with another surgical procedure. Laparoscopic procedures involving the renal pelvis/ureter that were combined with another procedure were included in group 3. Similarly, the control group was divided into three groups according to the urological organ involved. The parameters in each group were then compared with the control groups who had undergone unilateral laparoscopic adrenalectomy, consisting of 35 patients (group 1c), unilateral laparoscopic nephrectomy with 51 patients (group 2c) and unilateral laparoscopic ureterolithotomy consisting of 18 patients (group 3c), respectively.

The computerised database of these patients was analysed with respect to the operative time, blood loss, hospital stay, complications and cost analysis. The student t test was used for statistical analysis of the continuous variables. The operative duration was defined as the time taken from the placement of the first port to the closure of the last port and this also included the time spent in changing the position of the patient for bilateral procedures.

The various indications for simultaneous procedures are listed in [Table 1].

In group 1, patients with suspected Cushing's syndrome and phaeochromocytoma underwent complete preoperative evaluation, with urine and serum biochemistry. Contrast enhanced computed tomography scan (CECT) or Magnetic resonance imaging was used for imaging the adrenal gland.

Preoperatively, all patients with suspected phaeochromocytoma were hydrated well after insertion of a central line, and adequate alpha and beta blockers were given to control the blood pressure. Patients in group 2 had been evaluated with CECT abdomen to establish a diagnosis of renal mass and also to assess the local extent of the tumour. In group 3, patients with urolithiasis were evaluated with renal function tests, urine cultures, X-rays, ultrasound abdomen and intravenous urograms.

Coexisting medical morbid conditions, such as, coronary heart disease, severe obstructive airway disease and severe renal failure were considered as relative contraindications to perform a combined laparoscopic procedure.

Any variations in the port placement and extra ports, if needed, were made according to the surgical procedure. Patient position was changed intraoperatively for contralateral procedures. For patients in whom the expected operative duration was long, the end tidal carbon dioxide levels (ETCO ₂ ) were serially monitored during the procedure.

The advices and services of the other specialists, such as, the surgical gastroenterologist, endocrinologist and critical care anaesthesiologist were requested as and when required.

Results

Of a total of 534 patients who underwent laparoscopic procedures during the five years, 32 patients underwent 64 concomitant laparoscopic surgeries. [Table 2] shows the details of simultaneously performed procedures in the study groups as well as control groups.

The most common operation performed was laparoscopic adrenalectomy (n = 34) done in 18 patients. Sixteen patients underwent bilateral simultaneous laparoscopic adrenalectomy and the other two had unilateral adrenalectomy combined with other laparoscopic procedures. The most common indication for laparoscopic adrenalectomy in group 1 was Cushing's syndrome (including Cushing's disease). Three of the patients underwent total bilateral laparoscopic adrenalectomy for bilateral pheochromocytoma and two of them were part of the multiple Endocrine Neoplasia Syndrome.

Laparoscopic nephrectomy including simple, radical or heminephrectomy (n = 13) was the second most common procedure. Four patients in group 2 underwent simultaneous bilateral pretransplant nephrectomy for uncontrolled hypertension, which was followed four weeks later by allograft renal transplantation. In group 3, four of the patients underwent laparoscopic procedures for urolithiasis, while one underwent a laparoscopic dismembered pyeloplasty. Of the 64 concomitant laparoscopic procedures analysed, only five were for non-urologic pathology (three - cholecystectomies, one - oophorectomy and one - hernia repair).

A majority of the procedures were performed using the transperitoneal approach; the retroperitoneal approach was used in only eight procedures. These were all right-sided and included four pre-transplant nephrectomies, two adrenalectomies, deroofing of a renal cyst and a ureterolithotomy.
The mean operative duration, mean blood loss, mean duration of hospital stay and the mean expenditure in the three groups and their controls are shown in [Table 3].

The operative duration in group 1 was almost twice that in group 1c ( P = 0.012), which was statistically significant. However, patients in groups 2 and 3 had comparable operative durations with respect to their control arms. Also in our series, the mean estimated blood loss was comparable to that of the respective control arms in each group. The mean postoperative hospital stay was significantly prolonged in those who underwent concomitant procedures with laparoscopic adrenalectomy ( P = 0.025), while it was comparable in the other two groups.

The mean value of ETCO ₂ for combined procedures was 36 mm Hg. Only one female patient with Cushing's syndrome had a high level of ETCO ₂ and she required overnight ventilation. Oral intake was started in the postoperative period according to the surgical procedure and the associated morbidity of the patient. In most cases, oral liquid intake was resumed within four hours of the termination of surgery and normal diet was started on the first postoperative day.

Three patients had postoperative pyrexia due to atelectasis, which improved with chest physiotherapy, steam inhalation and appropriate antibiotics. One patient with bilateral adrenalectomy for Cushing's syndrome developed reactive pleural effusion, which subsided without aspiration. Another patient had developed chylous leakage a week after bilateral laparoscopic adrenalectomy for bilateral phaeochromocytomas. There was no conversion to open and no mortality in our series.

Discussion

Laparoscopy has emerged as an advanced tool for the newer generation of urologists to treat various urological diseases. Early postoperative recovery, early return to work and better cosmesis make laparoscopy an attractive option for patients as well as for surgeons. These benefits have now been extended for the performance of combined procedures either for two different diseases or for a bilateral presentation of the same disease. More expertise, skills and hands-on training are required to accomplish the task.

If two procedures are performed simultaneously, not only do patients have the advantage of minimal access surgery, but they also have a single hospital admission, preoperative evaluation and anaesthesia exposure.

Molmenti et al. , ^[11] reported five cases of laparoscopic donor nephrectomy combined with other surgical procedures such as adrenalectomy, cholecystectomy, colposuspension and liver biopsy. These patients did not have a statistically significant difference in operative time, blood loss or length of hospital stay. In another article, Schwartz et al. , ^[10] described three patients who underwent laparoscopic adrenalectomy in conjunction with simultaneous renal surgery and reported acceptable operative time and hospital stay with no increase in complications.

Bilateral laparoscopic adrenalectomy is now the standard of treatment for patients with Cushing's syndrome. ^[9] Simultaneous laparoscopic removal of both adrenals has hastened the recovery and reduced wound-related complications, thereby making laparoscopy preferable to the open approach in this subset of patients. ^[12] Shinbo et al. , ^[13] reported bilateral simultaneous adrenalectomy in a case of pituitary independent macronodular adrenal hyperplasia with less morbidity and early recovery from surgery. In a large series of 39 patients, Thompson et al. , ^[14] found that laparoscopic bilateral adrenalectomy was a safe and effective treatment option for Cushing's disease, with a majority of the patients experiencing considerable improvement in their symptoms and quality of life. Eleven patients in our series underwent bilateral simultaneous laparoscopic adrenalectomy with no significant increase in morbidity as compared to those who underwent unilateral adrenalectomy.

The simultaneous laparoscopic approach for pre- transplant nephrectomy has drastically reduced the waiting period for renal transplantation in patients with end-stage renal disease and uncontrolled hypertension. Wagner et al. , ^[15] analysed 15 patients who underwent bilateral nephrectomy for autosomal dominant polycystic kidney disease with end-stage renal failure and found that the median time from nephrectomy to living donor transplantation was 124 days, which was statistically a significant variable. However, Ismail et al. , ^[16] reported that 63.6% of his patients who underwent simultaneous laparoscopic bilateral native nephrectomy had complications, such as, incisional hernia, urinary fistula, enterocutaneous fistula and so on, which needed an additional surgical procedure. We did not encounter any major complications in this subset of patients.
In our series, the operative duration for combined urological procedures was slightly higher than the unilateral procedures, but this in no way affected the complication rate or morbidity. There were no significant increases in blood loss or hospital stay between these groups. In fact it can safely be assumed that combined procedures have reduced the need for a second anaesthesia, thereby reducing the total operative morbidity.
As we use laparoscopic instruments, the cost of the procedure has to be given much importance from the patient's perspective. In our series, combined procedures had drastically reduced the total expenses when compared to cost of two procedures at two different times.

Conclusion

When compared with a historical cohort of patients undergoing a single laparoscopic procedure, those undergoing simultaneous laparoscopic procedures did not experience a significant increase in perioperative morbidity, duration of hospitalisation or expenses. Provided the basic surgical principles and indication for simultaneous procedures were followed, more patients could enjoy the benefits of minimal access surgery.

Our series is definitely biased in the sense that patients expected to have a high risk of perioperative morbidity during concomitant surgery were operated in multiple sessions. A randomised controlled trial to compare single versus multiple staged surgeries for concomitant pathologic conditions is probably unethical. Hence, the conclusion that could be drawn is that concomitant laparoscopic urologic procedures are feasible in the good risk patient; concomitant surgery reduces the cost and morbidity of another admission and another surgery and reduces the associated anxiety of the patients. Two simultaneous laparoscopic surgeries in a single setting are better than two laparoscopic surgeries done separately.

References

1.
Wadhwa A, Chowbey PK, Sharma A, Khullar R, Soni V, Baijal M. Combined procedures in laparoscopic surgery. Surg Laparosc Endosc Percutan Tech 2003;13:382-6. 

2.
Kamer E, Unalp HR, Derici H, Tansug T, Onal MA. Laparoscopic cholecystectomy accompanied by simultaneous umbilical hernia repair: A retrospective study. J Postgrad Med 2007;53:176-80.    [PUBMED] 

3.
Nichitailo ME, Skums VV, Diachenko AN, Litvinenko AN, Ogorodnik PV, Galochka IP, et al . Simultaneous operations during laparoscopic cholecystectomy. Klin Khir 2004;2:5-7. 

4.
Zilberstein B, Pajecki D, Andrade CG, Eshkenazy R, Garcia de Brito AC, Gallafrio ST. Simultaneous gastric banding and cholecystectomy in the treatment of morbid obesity: Is it feasible? Obes Surg 2004;14:1331-4. 

5.
Watanabe Y, Miyauchi K, Horiuchi A, Kikkawa H, Kusunose H, Kotani T, et al . Concomitant laparoscopic splenectomy and cholecystectomy as an effective and minimally invasive treatment of pyruvate kinase deficiency with gallstones. Surg Endosc 2002;16:1495. 

6.
Gupta NP, Kumar R, Tandon S. Simultaneous laparoscopic adrenalectomy for pheochromocytoma and dismembered pyeloplasty for uretero-pelvic junction obstruction. J Laparoendosc Adv Surg Tech A 2005;15:405-7. 

7.
Rojas D, Rosales A, Palou J, Pascual X, Salvador J, Villavicencio H. Bilateral laparoscopic nephrectomy for renal cancer. Arch Esp Urol 2004;57:844-7. 

8.
Flasko T, Tallai B, Varga A, Toth C, Salah MA. Single-session laparoscopic radical and contralateral partial nephrectomy. J Laparoendosc Adv Surg Tech A 2005;15:322-4. 

9.
Porpiglia F, Fiori C, Bovio S, Destefanis P, Alμ A, Terrone C, et al . Bilateral adrenalectomy for Cushing's syndrome: A comparison between laparoscopy and open surgery. J Endocrinol Invest 2004;27:654-6.  

10.
Schwartz BF. Laparoscopic adrenalectomy with simultaneous management of renal pathology. BJU Int 2004;93:417-9. 

11.
Molmenti EP, Pinto PA, Montgomery RA, Su LM, Kraus E, Cooper M, et al . Concomitant surgery with laparoscopic live donor nephrectomy. Am J Transplant 2003;3:219-23. 

12.
Fernαndez-Cruz L, Sαenz A, Benarroch G, Sabater L, Taurα P. Total bilateral laparoscopic adrenalectomy in patients with Cushing's syndrome and multiple endocrine neoplasia (IIa). Surg Endosc 1997;11:103-7. 

13.
Shinbo H, Suzuki K, Sato T, Kageyama S, Ushiyama T, Fujita K. Simultaneous bilateral laparoscopic adrenalectomy in ACTH-independent macronodular adrenal hyperplasia. Int J Urol 2001;8:315-8. 

14.
Thompson SK, Hayman AV, Ludlam WH, Deveney CW, Loriaux DL, Sheppard BC. Improved quality of life after bilateral laparoscopic adrenalectomy for Cushing's disease: A 10-year experience. Ann Surg 2007;245:790-4. 

15.
Wagner MD, Prather JC, Barry JM. Selective, concurrent bilateral nephrectomies at renal transplantation for autosomal dominant polycystic kidney disease. J Urol 2007;177:2250-4.  

16.
Ismail HR, Flechner SM, Kaouk JH, Derweesh IH, Gill IS, Modlin C, et al . Simultaneous vs. sequential laparoscopic bilateral native nephrectomy and renal transplantation. Transplantation 2005;27:1124-7. 

Tables

[Table 1],  [Table 2],  [Table 3]

From http://www.journalofmas.com/article.asp?issn=0972-9941;year=2009;volume=5;issue=3;spage=67;epage=71;aulast=Maurya

Development of a Disease-Specific Quality of Life Questionnaire in Addison's Disease

Kristian Løvås*, Suzanne Curran, Marianne Øksnes, Eystein S. Husebye, Felicia A. Huppert,  and V. Krishna K. Chatterjee

Department of Medicine (K.L., S.C., V.K.K.C.), University of Cambridge, Cambridge CB2 0QQ, United Kingdom; Institute of Medicine (K.L., M.Ø., E.S.H.), University of Bergen, 5020 Bergen, Norway; Department of Medicine (K.L., E.S.H.), Haukeland University Hospital, 5021 Bergen, Norway; and Department of Psychiatry (F.A.H.), University of Cambridge, Cambridge CB2 2QQ, United Kingdom

* To whom correspondence should be addressed. E-mail: Kristian.lovas@helse-bergen.no.

Context: Patients with Addison's disease reproducibly self-report impairment in specific dimensions of general well-being questionnaires, suggesting particular deficiencies in health-related quality-of-life (HRQoL).

Objective: We sought to develop an Addison's disease-specific questionnaire (AddiQoL) that could better quantify altered well-being and treatment effects.

Design, Setting, Patients, Intervention, and Outcomes: We reviewed the literature to identify HRQoL issues in Addison's disease and interviewed patients and their partners in-depth to explore various symptom domains. A list of items was generated, and nine expert clinicians and five expert patients assessed the list for impact and clarity. A preliminary questionnaire was presented to 100 Addison's outpatients; the number of items was reduced after analysis of the distribution of the responses. The final questionnaire responses were assessed by Cronbach's {alpha} and Rasch analysis.

Results and Interpretation: Published studies of HRQoL in Addison's disease indicated reduced vitality and general health perception and limitations in physical and emotional functioning. In-depth interviews of 14 patients and seven partners emphasized the impact of the disease on the emotional domain. Seventy HRQoL items were generated; after the expert consultation process and pretesting in 100 patients, the number of items was reduced to 36. Eighty-six patients completed the final questionnaire; the responses showed high internal consistency with Cronbach's {alpha} 0.95 and Person Separation Index 0.94 (Rasch analysis).

Conclusions: We envisage AddiQoL having utility in trials of hormone replacement and management of patients with Addison's disease, analogous to similar questionnaires in GH deficiency (AGHDA) and acromegaly (AcroQoL).

 

From http://jcem.endojournals.org/cgi/content/abstract/jc.2009-1711v1

(Addison’s) A piece of presidential history solved the puzzle

By Sandra G. Boodman
Special to the Washington Post
Tuesday, December 15, 2009

As she lay in a heap, trying to figure out how badly she had hurt herself falling headfirst down a flight of stairs in the middle of the night, Rebecca Woodings grasped just how sick she really was.

For months doctors had been ratcheting up the medicines used to treat her intractable allergies. At one point she was taking 10 drugs a day and getting allergy shots. An economist who works for a large Washington law firm, Woodings, 49, told doctors she was tired; she assumed her fatigue was a consequence of her allergies, which were also causing a persistent cough. She did not tell them she was so exhausted she had to sit on the sidewalk while waiting for a bus and couldn't stand long enough to cook a meal.

Hours before she tumbled down the stairs of her Takoma Park home last June, an astute pulmonologist had figured out what was wrong -- and it had nothing to do with her lungs. That night, as Woodings tried to move the wrist she had broken in the fall, she focused on her 6-year-old son, realizing that if she had smacked her head she could have died. "I kept thinking, what would have happened to my child?"

In the fall of 2008 Woodings began feeling unusually tired. Walking less than a mile to the Metro in the morning made her break into a sweat. "It was very tiring," she said, and she recalled feeling puzzled. "I'm not terribly out of shape and I'm not overweight." Once on the Metro, Woodings made sure to get a seat; standing for 20 minutes was unthinkable.

During her annual checkup in November, her long-time internist at George Washington University discovered a Vitamin D deficiency and prescribed a short course of high-dose supplements.

By December, the fatigue was worse. Woodings had to sit down in the middle of a hymn during a church service. "All these little white-haired people around me are standing, and I couldn't," she recalled. When she mentioned the incident to a friend who works at the National Institutes of Health, she was told the symptoms sounded like a heart attack. Alarmed, Woodings immediately headed to a nearby emergency room, where an EKG and a chest X-ray showed that her heart was fine and her lungs were clear. Her father, a retired physician, suggested that maybe an antihistamine was causing her fatigue. Woodings stopped taking it and felt slightly more energetic.

By February, she was forced to sleep propped up on pillows and was taking a prescription cough syrup, which had little effect. The mother of a typically energetic kindergartner, she had started falling into bed around 8:30, when her son did. One night, she was so tired she told him to put himself to bed and crawled into bed at 8. Her allergist began administering allergy shots, which didn't help. Another doctor -- not her regular internist -- suggested she cut back on her sleep and get more exercise. Woodings replied that she was so tired she worried she might fall off a treadmill.

Routinely she arrived at the office at 9 a.m., already worn out. "It's really difficult to talk about being exhausted at a law firm," she said. "It sounds wimpy," so she didn't mention it.

In March, when she was handed a demanding new assignment with multiple deadlines, two new symptoms surfaced: Woodings began retching unpredictably -- "that damn cough," she remembered thinking -- and developed ferocious leg cramps at night. By then she noticed another peculiarity: Although she literally could not stand long enough to wait for a light to change while crossing the street, she could manage if she kept moving, walking slowly in a circle.

In early April, she went back to the allergist. He diagnosed a bad sinus infection and doubled the medications she was taking to 10 per day, including a short course of prednisone, a corticosteroid sometimes used to treat severe sinus infections.

After the first day, Woodings said, she felt markedly better. A week later the cough had disappeared and her energy slowly returned.

But by Memorial Day the fatigue was back and Woodings realized her problem wasn't allergies. She had stopped taking the allergy drugs, deciding that they might be the cause; her cough was gone. Woodings called her internist, whom she had not seen in six months. The doctor was heading out of town and Woodings decided to wait until her return rather than see a covering physician. In the meantime her physician ordered several tests, including those for Lyme disease and HIV, as well as CT scans of her lungs and sinuses.

On June 5, Woodings was told she had a possible bacterial infection in her lungs -- but not tuberculosis -- and was referred to GWU pulmonologist Susan Hasselquist. When she called to make an appointment, she was told that Hasselquist's first opening was a month away.

Desperate, Woodings decided to lie. "I said, 'I can't wait. The potential diagnosis is active TB.' " She was given an appointment for the next day.

On June 10 Woodings met with Hasselquist, who listened intently as Woodings recounted the events of the previous seven months. Unable to obtain a blood pressure using an automated cuff, Hasselquist measured it manually and found it was an alarmingly low 90/55. The lung specialist recalled being struck by how weak Woodings was: She lay down on the examining table while they talked because sitting up was too tiring. Hasselquist said she kept thinking of, and discarding, possible diagnoses. "I knew if we just kept talking I'd figure it out," she said.

Her eureka moment occurred when she zeroed in on Woodings's deep tan and asked her about it. Woodings, who is normally very fair, said that other people had remarked on it and that she hadn't spent much time in the sun.

Suddenly, Hasselquist said, she was certain what was wrong, a hunch triggered by photographs she'd seen of a ruddy-looking President John F. Kennedy, who had Addison's disease, a rare endocrine disorder that occurs when the adrenal glands become damaged and fail to produce enough cortisol and aldosterone, hormones vital for metabolic function. Most cases are the result of an autoimmune attack in which the immune system slowly destroys the adrenal glands. Woodings's dramatic improvement while taking prednisone, the steroid prescribed to treat her sinus infection, was a vital clue: It is one of the medicines used to treat Addison's.

Kennedy received an Addison's diagnosis at age 30; his sister, the late Eunice Kennedy Shriver, is also believed to have suffered from the disorder, which affects one to four of every 100,000 people, according to the National Institute of Diabetes and Digestive and Kidney Diseases.

Woodings had the classic symptoms of Addison's: progressive fatigue, muscle weakness, low blood pressure that falls further during a change in positions, and hyperpigmentation, which resembles a dark tan. The retching and legs cramps are also symptoms, although her allergies and cough are not.

Hasselquist did not mention her suspicion to Woodings because it would require confirmation from an endocrinologist. She said she suggested hospitalizing Woodings because she was so weak. When Woodings declined, Hasselquist warned her against standing up too quickly, which could cause dizziness.

After the appointment with Hasselquist, Woodings went straight home, ordered a pizza and went to bed. She awoke several hours later and headed for the bathroom to urinate. She remembers feeling dizzy, and then realizing she was at the bottom of the stairs, her wrist shattered. She managed to get up, call 911 and wake her son. Doctors in the ER set her wrist, told her to see an orthopedist because she would need surgery, then sent her home.

A few days later GWU endocrinologist Michael Irwig, to whom Hasselquist referred Woodings, confirmed the Addison's diagnosis. He prescribed prednisone and another drug Woodings will have to take for the rest her life to replace the hormones her body no longer produces.

Within a few weeks, Woodings said, she felt much better. Her energy level returned to normal, as did her blood pressure. Her tan is fading, and surgery on her wrist was successful.

"I can't fault any of the doctors," Woodings said, adding that she believes she should have called her internist early on, instead of consulting other physicians. "I think I could have described my condition a little better. I never said, 'I have to sit on the sidewalk waiting for a bus,' but rather, 'I'm tired all the time.' "

If you have a Medical Mystery that has been solved, e-mail medicalmysteries@washpost.com. To read previous mysteries, go to http://www.washingtonpost.com/health.

From http://www.washingtonpost.com/wp-dyn/content/article/2009/12/14/AR2009121402863.html

~~~~~~~~~~~~~~~

Feedback:

Woman's tale of Addison's disease proves the value of primary-care physicians

Tuesday, December 22, 2009

Of primary importance

"A piece of presidential history solved the puzzle" [Dec. 15], about the lady found to have Addison's disease, points out how crucial it is to have a primary-care focus in evaluating patients. Often patients scramble through a maze of specialists, as she did, without a strong primary-care clinician coordinating care.

My hope is that health reform will recognize the essential perspective that primary-care physicians from family medicine, geriatrics and internal medicine bring to patient care. They can save patients and the health-care system heartache and money. It is the most challenging field in medicine and the most holistic.

Our system should provide incentives for new medical school graduates to join these fields and reward these physicians appropriately. These doctors work very, very hard. Good primary-care clinicians are worth their weight in gold.

Christine Butler

Coordinator, Palliative Care Service

Sibley Memorial Hospital

Washington

From http://www.washingtonpost.com/wp-dyn/content/article/2009/12/18/AR2009121803706.html

Suggesting Cushing’s to a Stranger

This post at http://blog.dustincurtis.com/amateur-diagnosis-a-dilemma reminded me of a topic we often discuss on the message boards.

That post said:

I saw a woman at Starbucks earlier today who almost certainly has Cushing’s Syndrome, a rare-ish debilitating disease that is curable with treatment. It has some very clear physical signs, like a “moon face”, a hump on the back, and central obesity with normal sized extremities. The woman I saw might not know she has it; thousands of people live in misery with undiagnosed Cushing’s for years. It can be fatal.

What is the right thing to do in a situation like this? Do you tap her on the shoulder and kindly tell her your amateur diagnosis, possibly saving her life, or do you let her go on her way, potentially living in misery?

I stared at her for about 10 seconds, thinking about what to do, and then left without saying anything.

Some of the symptoms of Cushing’s

So, if you saw someone with Cushing’s,what would *you* do?

~~~~~~~~~~~~~~~~~~~~~~

Some early responses from Facebook:

Would you tell a stranger they might have Cushing’s?

• Yes!!!

• I did…and it did not go over well. I recommended two ladies see an endo because they were obviously cushie. Both thought I was nuts and didn’t listen to me (that I know of.) One was a patient of my GI and she told me all her symptoms and it was classic Cushing’s-and she didn’t believe me. She told the doc I was nuts. I don’t know if I helped or hindered their quest for a diagnosis. It makes me think twice if I see someone that might have Cushing’s.

• Well, I think what we have to consider is that it really doesn’t matter what they think of us. At least they have heard the word and maybe, just maybe, will investigate it more.

• I know Jayne has had a lot of success talking to people she saw in the store. And, of course, Robin made us these wonderful cards. Scroll down http://www.cushings-help.com/documents.htm until you see “Spread The Word! Cushing’s Pocket Reference”

How about it?  Would you give someone a card or talk to them?

Harvey Cushing

A bit more about Dr. Harvey Cushing’s life from http://ile-bubulina.blogspot.com/2009/12/endovascular-techniques-in-management.html

In his biography of Cleveland native Harvey Cushing, John Fulton describes the fortuitous series of circumstances that conspired to create the specialty of neurological surgery.

The compulsive and competitive Dr Cushing trained as a surgeon under the precise tutelage of William Hallsted. On the recommendation of his friend and mentor, William Osler, Cushing spent the year following completion of his surgical residency traveling Europe. It was then, under the guidance of Professor Theodor Kocher in the laboratory of Professor Hugo Kronecker in Berne, Switzerland, that Cushing described the relationship between intracranial pressure and systemic blood pressure regulated by the vasomotor center in the medulla that would ultimately be known as the ‘Cushing reflex’. Prior to this time, vital signs (and in particular blood pressure) were not routinely charted during surgical procedures. Cushing continued his experiments as he toured Europe, performing studies in dogs in Professor Angelo Mosso’s laboratory in Turin, Italy. While in Italy, Cushing was serendipitously introduced to Scipione Riva-Rocci’s elegantly simple sphygmomanometer, which he promptly recognized as a significant addition to the operating room.

Upon his return home the combination of his compulsive personality, watchful (albeit indirect) management of systemic and intracranial pressure, and career-long obsession with hemostasis
(Cushing developed the silver hemoclip, and, with physicist W Bovie, introduced electrocoagulation) precipitated the beginning of neurosurgical practice.

There is more information about Dr Cushing here: http://www.cushings-help.com/harvey.htm

Cushie 12-Step Program

I “acquired” this from another site and changed the names to protect the innocent…

As you know many of us Cushies have had or have an addiction to Googling.

I suggest anyone who feels compelled to google symptoms go to the message boards to ask for support instead of typing these or any words such as "buffalo hump" in the google search engine. When this is done all roads lead to one thing...... You Eat Too Much!; You're Depressed! 

So, anyone who is about to hit enter on their computer which feeds their Google addiction.... go to the message boards to ask for help. One of the other Cushies who have achieved "Google sobriety" will help you down of the ledge.

1. Admit for now that you are powerless over your urge to Google.
2. Believe that a power greater than you (that would be other Cushies) can help you off that ledge
3. Decide to turn your "fingers" over to a higher power as you understand it.
4. Make a searching and fearless inventory of what you hope to gain from googling.
5. Admit to yourself and to another human being the exact nature of your addiction to Google.
6. Allow other Cushies to assist you when you are so scared you are thinking about googling symptoms.
7. Humbly ask for Xanax, Klonopin or Cortef in order to calm yourself from googling symptoms
8. Make a list of all the diseases you think you have or have had and survived and have a burning ceremony and then.... take a nap.
9. Cite all Google sites you have searched diseases on and delete them from your favorites/history.
10. When you start thinking....STOP..... do something else, like take an inventory of your test results.
11. Seek through prayer and/or meditation to improve your thought process. Do not travel to "OMG' or "What if" land (this is a serious suggestion).
12. Having had a spiritual awakening as a result of these steps, carry this message to all your Cushie friends and anyone else you know who has a Google addiction.

13. Now I know there isn't a 13th step, however, if you have noticed you are drinking too much wine or taking too many pills, please remember there are other 12 step programs for that, lol...

So, what about it - what are *your* suggestions to cure Google Addiction?

Psychosomatic aspects of Cushing’s syndrome

Journal
Reviews in Endocrine & Metabolic Disorders

Publisher
Springer Netherlands

ISSN
1389-9155 (Print) 1573-2606 (Online)

DOI
10.1007/s11154-009-9123-7

Subject Collection
Medicine

SpringerLink Date
Thursday, December 03, 2009

PDF (218.0 KB) | HTML | Free Preview

Psychosomatic aspects of Cushing’s syndrome

Nicoletta Sonino^{1, 2, 3} , Francesco Fallo⁴ and Giovanni A. Fava^{3, 5}

(1) 
Department of Statistical Sciences, University of Padova, Via Battisti 241, 35121 Padova, Italy

(2) 
Department of Mental Health, Padova, Italy

(3) 
Department of Psychiatry, State University of New York at Buffalo, Buffalo, NY, USA

(4) 
Department of Medical and Surgical Science, University of Padova, Padova, Italy

(5) 
Department of Psychology, University of Bologna, Bologna, Italy

Published online: 4 December 2009

Abstract  There has been growing interest in the psychosocial aspects of Cushing’s syndrome, such as the role of life stress as a pathogenetic factor, the association with affective disorders, and the presence of residual symptoms after treatment.

Interestingly, a temporal relationship between stressful life events and disease onset is relevant only to pituitary-dependent Cushing’s disease, and not to the pituitary-independent forms. A number of psychiatric and psychological disturbances may be associated with the active hypercortisolemic state, regardless of its etiology.

Within the high frequency of mood disorders (about 60%), major depression is the most common complication. Other psychopathological aspects include mania, anxiety disorders, psychological symptoms (demoralization, irritable mood, somatization) and cognitive impairment. Cognitive symptoms are associated with brain abnormalities (mainly loss of brain volume).

Quality of life may be seriously compromised during both active and post-treatment phases. Long-standing hypercortisolism may imply a degree of irreversibility of the pathological process. Recovery, thus, may be delayed and be influenced by highly individualized affective responses.

Outcomes of Cushing’s syndrome treatment are not fully satisfactory. Within its great complexity, a conceptual shift from a merely biomedical care to a psychosomatic consideration of the person and his/her quality of life appears to be necessary to improve effectiveness. It is time to translate the research evidence that has accumulated into clinical practice initiatives.

To patients who show persistence or even worsening of psychological distress upon adequate endocrine treatment psychiatric/psychological interventions should be readily available. Applying interdisciplinary expertise and addressing the needs for rehabilitation would markedly improve final outcome.

Keywords  Cushing’s syndrome - Psychosomatic medicine - Quality of life - Life events - Depression - Cognitive impairment

---

Nicoletta Sonino
Email: nicoletta.sonino@unipd.it

Fulltext Preview (Small, Large)

 

From http://www.springerlink.com/content/221628557322j613/

Tumor Volume of Growth Hormone-Secreting Pituitary Adenomas during Treatment with Pegvisomant: A Prospective Multicenter Study

Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2009-1239
Jan-Hendrik Buhk*, Sabine Jung, Marios Nikos Psychogios, Sophia Göricke, Sabine Hartz, Susanne Schulz-Heise, Randolf Klingebiel, Michael Forsting, Hartmut Brückmann, Arnd Dörfler, Martina Jordan, Michael Buchfelder,  and Michael Knauth
Department of Neuroradiology (J.-H.B., S.J., M.N.P., M.K.), University of Goettingen, D-37075 Goettingen, Germany; Department of Diagnostic and Interventional Radiology (J.-H.B.), University of Hamburg, D-20246 Hamburg, Germany; Department of Diagnostic and Interventional Radiology (S.G., M.F.), University of Essen, D-45147 Essen, Germany; Department of Neuroradiology (S.H., H.B.), University of Munich, D-81377 Munich, Germany; Departments of Neuroradiology (S.S.-H., A.D.) and Neurosurgery (M.B.), University of Erlangen-Nuremberg, D-91054 Erlangen Germany; Department of Neuroradiology (R.K.), Charité, Free University of Berlin, D-10117 Berlin, Germany; and ClinSupport, Clinical Trials and Marketing Support (M.J.), Erlangen, Germany
* To whom correspondence should be addressed. E-mail: jh.buhk@mac.com.

Context: Clinical and biochemical remission in acromegaly can frequently be achieved with the recombinant GH receptor antagonist pegvisomant, even when other treatments fail. However, increases in tumor volume have been reported.
Objective: Because previous studies suffer from inhomogenous magnetic resonance imaging (MRI) protocols, this prospective study examined the long-term course of adenoma volume during pegvisomant therapy by standardized MRI.

Design: Five centers in Germany participated. High-resolution MRI was performed at baseline and 6, 12, and 24 months after enrollment.

Setting/Patients: Patients were outpatients, and pegvisomant is third-line therapy in most of the cases.

Main Outcome Measures: The primary end point was tumor volume at 24 month follow-up, measured by a single, double-blinded rater.

Results: Forty-five of 61 patients completed 24 months' follow-up (73.8%). Tumor volume increase greater than 25% during the study was observed in three of 61 patients (4.9%), all during the first year of enrollment. All three patients had had octreotide treatment before initiation of pegvisomant; none of them had had radiotherapy. All volumetric findings were comparable with clinical radiological interpretations. ANOVA revealed no significant change in tumor volume after 24 months (n = 45).

Conclusions: This study shows that pegvisomant therapy infrequently coincides with tumor growth during long-term treatment of acromegaly. Because all significant tumor volume increases occurred during the first year, these changes might correlate to the change of medication and thus be the result of a rebound from somatostatin-induced shrinkage.

From http://jcem.endojournals.org/cgi/content/abstract/jc.2009-1239v1

Diagnosis and Treatment of Adrenal Tumors: A Single-Center Experience with 238 Cases

Abdul-Monem Gomha, Yasser Osman, Mohsen El-Mekresh, Mohamed Abou El-Ghar, Ibrahim Eraky
Urology Department, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt

Address of Corresponding Author

Urol Int 2009;83:433-437 (DOI: 10.1159/000251184)

---

 Key Words

• Adrenal mass
• Adrenalectomy

---

 Abstract

Objective: It was the aim of this study to review and analyze clinical data on the diagnosis and management of patients with adrenal masses. 

Patients and Methods: Between 1976 and 2005, 238 patients admitted to our institute with adrenal masses were reviewed. Incidence, clinical features, imaging technique findings, surgical approaches, morbidity and mortality, as well as pathological diagnoses were reported. 

Results: The series comprised 134 males and 104 females (mean age 33.3 ± 20.3 years). Right-sided masses were more common (63.4%), with a mean size of 7.7 ± 4 cm. Pain was the most frequent presenting symptom (53.4%), while 62 (26%) had a functional tumor. Incidentaloma was diagnosed in 49 patients (20.6%). Both computed tomography and magnetic resonance imaging showed a high diagnostic yield (sensitivities of 98.9 and 100%, respectively). Open adrenalectomy was performed in 153 patients (64.3%), while a laparoscopic approach was employed in 53 patients (22.3%). The intraoperative complication rate was 14.7%, the postoperative complication rate 6.1% and perioperative mortality 1.7%. Most of the excised masses were pheochromocytomas (26.4%).

Conclusions: Computed tomography is recommended as the first diagnostic modality to define and characterize adrenal masses. Laparoscopic adrenalectomy is currently replacing open surgery as the standard surgical management of adrenal masses.

Copyright © 2009 S. Karger AG, Basel

---

 Author Contacts

Yasser Osman, MD
Urology and Nephrology Center
Mansoura University
Mansoura (Egypt)
Tel. +20 50 226 2222, Fax +20 50 226 3717, E-Mail y_osman99@yahoo.com

---

 Article Information

Received: October 20, 2008
Accepted: December 9, 2008
Published online: December 08, 2009
Number of Print Pages : 5
Number of Figures : 1, Number of Tables : 3, Number of References : 20

 

From http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=251184&Ausgabe=253627&ProduktNr=224282

Ultrasound-assisted Microsurgery for Cushing's Disease

Exp Clin Endocrinol Diabetes : 
DOI: 10.1055/s-0029-1241207

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

U. J. Knappe¹, M. Engelbach², K. Konz³, H.-J. Lakomek⁴, W. Saeger⁵, R. Schönmayr⁶, W. A. Mann⁷

¹ Department of Neurosurgery, Johannes Wesling Klinikum, Minden, Germany
² German Clinic for Endocrinology, Frankfurt, Germany
³ Department of Endocrinology, Deutsche Klinik für Diagnostik, Wiesbaden, Germany
⁴ Department of Endocrinology, Johannes Wesling Klinikum, Minden, Germany
⁵ Department of Pathology, Marienkrankenhaus, Hamburg, Germany
⁶ Department of Neurosurgery, Dr. Horst Schmidt Klinik, Wiesbaden, Germany
⁷ Endokrinologikum Frankfurt am Main, Frankfurt, Germany

Abstract

Objective: Localization of microadenomas in Cushing's disease may be difficult as in up to 45% of patients sellar MRI fails to detect a pituitary tumor. Intraoperative transsphenoidal ultrasound may identify microadenomas as hyperechoic structures. We report on the first 18 consecutive cases with intraoperative use of a new device for direct contact high-frequency-ultrasound in patients with Cushing's disease.

Patients and technique: 18 patients (14 female, 4 male, age 24-71 years) with typical endocrinological findings for Cushing's disease were included in the study. One macroadenoma and 13 microadenomas were suspected or identified preoperatively by MRI. In 4 cases, two of them with recurrent disease, sellar MRIs were negative. During transsphenoidal microsurgery an end fire ultrasound-probe (B-mode frequency range 7.5-13 Mhz, field of view 5 mm, penetration 20 mm) was introduced after opening of sellar floor. The pituitary gland was scanned in direct contact to the capsule.

Results: In 13 out of 17 cases (77%) with later on proven microadenomas high-frequency-ultrasound identified the tumors as hyperechoic masses, including 3 of the 4 cases with negative preoperative MRI. In 2 cases ultrasound correctly localized the tumor at a site different from MRI finding (MRI false positive). In the macroadenoma, identification of the border between tumor and anterior pituitary gland was not possible. In all 18 patients postoperative early decline of serum cortisol to subnormal levels confirmed remission of hypercortisolism (100%). Other pituitary functions were unaltered in 17 cases (94%).

Conclusions: Intraoperative scanning of the pituitary gland with high-frequency-ultrasound probes may identify intrapituitary anatomy and pathologies even in MRI-negative cases. This may prevent extensive exploration of the gland with the risk of subsequent hypopituitarism.

Key words

Cushing's disease - intraoperative imaging - microadenoma - pituitary tumor - transsphenoidal surgery – ultrasound

From http://www.thieme-connect.de/ejournals/abstract/eced/doi/10.1055/s-0029-1241207

Epidemiology of adrenal crisis in chronic adrenal insufficiency – the need for new prevention strategies

European Journal of Endocrinology (2009) In press
DOI: 10.1530/EJE-09-0884
Copyright © 2009 by European Society of Endocrinology

Stefanie Hahner, Melanie Loeffler, Benjamin Bleicken, Christiane Drechsler, Danijela Milovanovic, Martin Fassnacht, Manfred Ventz, Marcus Quinkler and Bruno Allolio

S Hahner, Endocrinology and Diabetes Unit, University of Wuerzburg, Wuerzburg, D-97080 , Germany
M Loeffler, University of Wuerzburg, Endocrinology and Diabetes Unit, Würzburg, Germany
B Bleicken, Dept. of Medicine I, University of Wuerzburg, Würzburg, Germany
C Drechsler, Dept. of Nephrology, University of Würzburg, Würzburg, Germany
D Milovanovic, University of Wuerzburg, Endocrinology and Diabetes Unit, Würzburg, Germany
M Fassnacht, Dept. of Medicine I, University of Würzburg, Würzburg, Germany
M Ventz, Dept. of Medicine I, University of Wuerzburg, Würzburg, Germany
M Quinkler, Dept. of Medicine I, University of Wuerzburg, Würzburg, Germany
B Allolio, University of Wuerzburg, Endocrinology and Diabetes Unit, Würzburg, Germany

Correspondence: Stefanie Hahner, Email: hahner_s@medizin.uni-wuerzburg.de

Objective: Adrenal crisis (AC) is a life-threatening complication of adrenal insufficiency (AI). Here we evaluated frequency, causes and risk factors of AC in patients with chronic AI.

Methods: In a cross-sectional study 883 patients with AI were contacted by mail. 526 patients agreed to participate and received a disease specific questionnaire.

Results: 444 data sets were available for analysis (primary adrenal insufficiency, PAI n=254, secondary adrenal insufficiency, SAI n=190). 42% (PAI 47%, SAI 35%) reported at least one crisis. 384 AC in 6092 patient years were documented (frequency of 6.3 crises/100 patient years). Precipitating causes were mainly gastrointestinal infection and fever (45%) but also other stressful events (e.g. major pain, surgery, psychic distress, heat, pregnancy). Sudden onset of apparently unexplained AC was also reported (PAI 6.6%, SAI 12.7%). Patients with PAI reported more frequent emergency glucocorticoid administration (42.5% vs 28.4%, p=0.003)) Crisis incidence was not influenced by educational status, BMI, glucocorticoid dose, DHEA treatment, age at diagnosis, hypogonadism, hypothyroidism or growth hormone deficiency. In PAI, patients with concomitant non-endocrine disease were at higher risk of crisis (OR=2.02, 95% CI 1.05-3.89, p=0.036). In SAI, female sex (OR=2.18, 95%CI 1.06-4.5, p=0.035) and diabetes insipidus (RR=2.71, 95%CI 1.22-5.99, p=0.014) were associated with higher crisis incidence.

Conclusion: AC occurs in a substantial proportion of patients with chronic AI, mainly triggered by infectious disease. Only a limited number of risk factors suitable for targeting prevention of AC were identified. These findings indicate the need for new concepts of crisis prevention in patients with AI.

From http://www.eje.org/cgi/content/abstract/EJE-09-0884v1

Diagnosis, management and therapeutic outcome in prepubertal Cushing’s disease

European Journal of Endocrinology (2009) In press
DOI: 10.1530/EJE-09-0509
Copyright © 2009 by European Society of Endocrinology

Renuka Dias, Anitha Kumaran, Li Chan, Lee Martin, Fary Afshar, Michael Matson, P N Plowman, John Monson, Michael Besser, Ashley Grossman, Martin Savage and H L Storr

R Dias, Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
A Kumaran, Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
L Chan, Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
L Martin, Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
F Afshar, Neurosurgery, Barts and the London School of Medicine and Dentistry, London, United Kingdom
M Matson, Radiology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
P Plowman, Radiotherapy, Barts and the London School of Medicine and Dentistry, London, United Kingdom
J Monson, Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
M Besser, Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
A Grossman, Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
M Savage, Paediatric Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom
H Storr, Endocrinology, Barts and the London School of Medicine and Dentistry, London, United Kingdom

Correspondence: Renuka Dias, Email: r.dias@qmul.ac.uk

Objectives: Cushing’s disease (CD) in prepubertal children is very rare and presents important diagnostic and therapeutic challenges. We report experience of the management of this subpopulation of CD patients.

Study Design/ Methods: Retrospective patient case note review

Results: Between 1985 and 2008, seventeen prepubertal children (13M, 4F), aged 5.7 to 14.1 yr presented to our centre for diagnosis and management of CD. All children had subnormal linear growth and excessive weight gain at presentation. A high proportion (85% of males, 75% of females) had evidence of excessive virilisation. Striae or hypertension were seen in 41% of patients. The investigation with highest sensitivity (100%) for CD was excessive increase of serum cortisol to IV CRH (mean increase 113%). Pituitary imaging performed in all patients showed poor concordance with findings at surgery (31%). In contrast BSIPSS, performed in 11/16 subjects showed a high correlation with surgical findings (91%). In 16 patients, transsphenoidal selective adenomectomy (TSS) achieved a cure rate of 44%. However, in the 11 patients who had pre-operative BSIPSS the cure rate was 64%. 9/16 patients who were not cured by TSS received external pituitary radiotherapy (RT).

Conclusions: Prepubertal CD had distinctive features with increased frequency in males, abnormal auxology and excessive virilisation. The cortisol response to IV CRH administration was particularly exuberant and contributed to diagnosis. BSIPSS was much more helpful than pituitary imaging in localisation of the microadenoma and was associated with improved cure rate by TSS.

From http://www.eje.org/cgi/content/abstract/EJE-09-0509v1

Novartis seeks to expand cancer drug portfolio

By Alaric DeArment

BASEL, Switzerland (Dec. 11) Novartis hopes to maintain what it calls its leading global position in cancer treatments with a wave of regulatory submissions in the coming year, the Swiss drug maker announced at a recent investors meeting.

By the end of the 2009, the company plans to file regulatory approval applications seeking to expand the use of Tasigna (nilotinib) and Zometa (zoledronic acid) as treatments for various cancers and make as many as five other regulatory submissions in 2010 for Afinitor (everolimus) and drugs in clinical trials.

“We have a productive and innovative pipeline that holds promise for many patients,” Novartis Pharmaceuticals Division CEO Joe Jimenez said. “The benefits of our sustained R&D investments are reflected in the nearly 30 major regulatory approvals achieved so far in 2009 in the U.S., Europe, Japan and China. A further 27 projects are currently in late-stage clinical trials, while eight more projects are awaiting regulatory decisions.”

Drugs in clinical development include SOM230 (pasireotide), for which Novartis will seek approval in 2010 as a treatment for Cushing’s disease, carcinoid tumors and acromegaly, and LBH589 (panobinostat), for which the company will seek approval that same year as a Hodgkins lymphoma treatment.

From http://drugstorenews.com/story.aspx?id=125727&menuid=787

(Ectopic) Cushing's syndrome associated with an islet-cell tumour of the pancreas in a boy aged 2 years.

J. H. Burkinshaw, D. O'Brien, and J. E. Pendower

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.8M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

525

526

527

528

529

530

531

Images in this article

Fig. 1
on p.525

Fig. 2
on p.526

Fig. 3
on p.527

Fig. 4
on p.527

Fig. 5
on p.528

Fig. 6
on p.528

Fig. 7
on p.529

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

• ALLOTT EN, SKELTON MO. Increased adrenocortical activity associated with malignant disease. Lancet. 1960 Aug 6;2(7145):278–284. [PubMed]
• BAGSHAWE KD. Hypokalaemia, carcinoma and Cushing's syndrome. Lancet. 1960 Aug 6;2(7145):284–287. [PubMed]
• BALLS KF, NICHOLSON JT, GOODMAN HL, TOUCHSTONE JC. Functioning islet-cell carcinoma of the pancreas with Cushing's syndrome. J Clin Endocrinol Metab. 1959 Sep;19:1134–1143. [PubMed]
• PIERRE-BOURGEOIS, ROGE J, CLEMENT D, MARTIN E, DESCAMPS J. [Hypercorticism syndrome and pancreatic cancer of the Langerhans type.]. Bull Mem Soc Med Hop Paris. 1959 Jun 19;75:665–671. [PubMed]
• DEL CASTILLO EB, TRUCCO E, MANZUOLI J. Maladie de Cushing et cancer du pancréas. Presse Med. 1950 Jul 5;58(43):783–785. [PubMed]
• CHRISTY NP. Adrenocorticotrophic activity in the plasma of patients with Cushing's syndrome associated with pulmonary neoplasms. Lancet. 1961 Jan 14;1(7168):85–86. [PubMed]
• Friedman M, Marshall-Jones P, Ross EJ. Cushing's syndrome: adrenocortical hyperactivity secondary to neoplasms arising outside the pituitary-adrenal system. Q J Med. 1966 Apr;35(138):193–214. [PubMed]
• JARETT L, LACY PE, KIPNIS DM. CHARACTERIZATION BY IMMUNOFLUORESCENCE OF AN ACTH-LIKE SUBSTANCE IN NONPITUITARY TUMORS FROM PATIENTS WITH HYPERADRENOCORTICISM. J Clin Endocrinol Metab. 1964 Jun;24:543–549. [PubMed]
• MARKS V, SAMOLS E, BOLTON R. HYPERINSULINISM AND CUSHING'S SYNDROME. Br Med J. 1965 May 29;1(5447):1419–1420. [PubMed]
• MEADOR CK, LIDDLE GW, ISLAND DP, NICHOLSON WE, LUCAS CP, NUCKTON JG, LUETSCHER JA. Cause of Cushing's syndrome in patients with tumors arising from "nonendocrine" tissue. J Clin Endocrinol Metab. 1962 Jul;22:693–703. [PubMed]
• NICHOLS J, GOURLEY W. Adrenal weight-maintaining corticotropin in carcinoma of lung. JAMA. 1963 Aug 31;185:696–698. [PubMed]
• O'Riordan JL, Blanshard GP, Moxham A, Nabarro JD. Corticotrophin-secreting carcinomas. Q J Med. 1966 Apr;35(138):137–147. [PubMed]
• ROSENBERG AA. Fulminating adrenocortical hyperfunction associated with islet-cell carcinoma of the pancreas; case report. J Clin Endocrinol Metab. 1956 Oct;16(10):1364–1373. [PubMed]
• Ross EJ, Marshall-Jones P, Friedman M. Cushing's syndrome: diagnostic criteria. Q J Med. 1966 Apr;35(138):149–192. [PubMed]

---

Articles from Archives of Disease in Childhood are provided here courtesy of

BMJ Group

From http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2019792/

Adrenal Insufficiency: University company wins healthy £300k for new Cardiff-based drug

A UNIVERSITY spin-out venture yesterday won a £300,000 investment to support the commercialisation of its product.

Fusion IP, the university commercialisation company which turns university research into business, is investing the money into Diurnal, an innovative, early stage Fusion portfolio company from the University of Sheffield.

Cardiff-based Diurnal is developing a novel approach to drug delivery which will help patients suffering from reduced cortisol and testosterone levels.

The investment is part of a £600,000 funding round in which Finance Wales has also invested £300,000 under its memorandum of understanding with Fusion. Diurnal will have a post-money valuation of £2m.

Diurnal has developed a delayed and sustained release therapy to deliver hydrocortisone in a manner that mimics the body’s normal circadian rhythm – the body’s natural 24 hour hormone cycle.

This therapeutic approach has the potential to help patients with deficiencies in steroid hormones, testosterone, thyroid hormones and associated conditions by regulating metabolism, growth development and puberty, tissue function and in determining mood.

Each of these deficiencies requires life-long treatment and Diurnal’s approach to drug delivery has the potential to drastically improve patients’ lives, according to the company.

Working closely with Penn Pharma, the Tredegar-based pharmaceutical services company, and Simbec Research in Merthyr Tydfil, Diurnal will use the funding to continue to develop its new formulation approach to endocrine therapy and to complete phase one clinical trials of its lead product Chronocort, for adrenal insufficiency in the first half of next year.

The product has already received two related Orphan Drug designations from the European Medicines Agency, which affords 10 years of market exclusivity after the grant of marketing authorisation in Europe.

Martin Whitaker, general manager at Diurnal, said: “Diurnal’s product pipeline has the potential to help many patients with hormone deficiencies that disrupt the body’s natural clock.

“Our lead compound Chronocort is focused on delivering a delayed and sustained release therapy. Following positive pre-clinical results and today’s fundraising, Chronocort is poised to enter phase one clinical trials next year.

“In addition, it has significant market potential and has already received Orphan Drug Designation potentially giving it market exclusivity in Europe.”

Following the fundraising Fusion will have a 51.6% shareholding in Diurnal.

David Baynes, chief executive officer of Fusion IP, said: “Diurnal’s endocrine therapies have great potential for patients suffering from hormone deficiencies.

“Taking Chronocort into phase I clinical trials next year is a major step forward for Diurnal and we are delighted to see the company making such positive progress.”

Jocelyn Brown, Associate at Finance Wales, said: “This latest funding round accelerates Diurnal’s commitment to creating niche therapeutics targeting areas of greatest unmet patient need.

“The continuing success of Diurnal is underpinned by their strong partners within the Welsh biosciences community, and we’re pleased to be investing in such a dynamic, forward-looking company.”

 

From http://www.walesonline.co.uk/business-in-wales/business-news/2009/12/08/university-company-wins-healthy-300k-for-new-cardiff-based-drug-91466-25341981/

ClinicalTrialWatch.com's Featured Study: The Seismic Study

The SEISMIC study is a Phase III, multi-center study of Corlux for the treatment of endogenous Cushing's Syndrome.

It is a 6-month study with daily dosing of the investigational drug, Corlux. It is open label, that is, no placebo is required. The protocol includes about 13 clinic visits. After the 6 month treatment period is over, patients return for a 6-week follow up visit.

The study will enroll 50 Cushing's Syndrome patients at approximately 20-25 sites in the US.

The SEISMIC study is seeking patients who require medical treatment for endogenous Cushing's Syndrome due to ectopic ACTH syndrome, adrenal tumors, adrenal hyperplasia, or Cushing's disease when they are not candidates for pituitary surgery or who have failed or recurred after pituitary surgery. Please see detailed eligibility criteria.

See if you are a candidate for this breakthrough Cushing's Syndrome clinical trial

Cushings Articles

Cushing's Syndrome Clinical Trial Qualification Questionnaire

On Dec 05, 2008, Adrian wrote:

The SEISMIC study is seeking patients who require medical treatment for endogenous Cushing's Syndrome due to ectopic ACTH syndrome, adrenal tumors, adrenal hyperplasia, or Cushing's disease when they are not candidates for pituitary surgery or who have failed or recurred after pituitary surgery.

Medical Professionals Interested in Cushing's Syndrome

On Jul 14, 2008, ClinicalTrialWatch Editor wrote:

Medical Professionals: Learn More About The Cushing's Syndrome Clinical Study Study Purpose The SEISMIC Study is a Phase III open label US based clinical research trial designed to test mifepristone in the treatment of the clinical manifestations of endogenous Cushing's ...

SEISMIC Study Eligibility Criteria

On Jul 08, 2008, ClinicalTrialWatch Editor wrote:

SEISMIC Study Main Inclusion Criteria Patients please take the questionnaire Cushing's Syndrome Clinical Trial Qualification Questionnaire to see if you prequalify for the study. Physicians and health care providers view the inclusion and exclusion criteria below and read our ...

Additional Publications and Research

On Jul 07, 2008, ClinicalTrialWatch Editor wrote:

External Publications about Cushing's Syndrome Sartor O, Cutler GB Jr. Mifepristone: treatment of Cushing's syndrome. Clin Obstet Gynecol. 1996 Jun;39(2):50610. Review. http://www.ncbi.nlm.nih.gov/pubmed/8734015?dopt=Abstract Johanssen S, Allolio ...

Friends and Family of Cushing's Syndrome Patients

On Jul 07, 2008, ClinicalTrialWatch Editor wrote:

you know someone suffering with Cushing's Syndrome and believe they may be a candidate for this Phase III clinical trial, please tell them about the SEISMIC Study by sending them a link to the Cushing's Syndrome Clinical Trial Qualification Questionnaire. Please also ...

About Cushing's Syndrome

On Jul 07, 2008, ClinicalTrialWatch Editor wrote:

What is Cushing's Syndrome? Cushing's syndrome was originally described by Harvey Cushing in 1932 and is a relatively rare but serious condition. It is caused by a prolonged exposure to elevated levels of the stress hormone cortisol. Cortisol is produced and released by the adrenal glands; it is necessary for many bodily ...

Articles

Effectiveness of cabergoline in monotherapy and combined with ketoconazole in the management of Cushing’s disease

Journal
Pituitary

Publisher
Springer Netherlands

ISSN
1386-341X (Print) 1573-7403 (Online)

DOI
10.1007/s11102-009-0209-8

PDF (235.5 KB) | HTML | Free Preview

Effectiveness of cabergoline in monotherapy and combined with ketoconazole in the management of Cushing’s disease

Lucio Vilar^{1, 2, 4} , Luciana A. Naves³, Monalisa F. Azevedo³, Maria Juliana Arruda¹, Carla M. Arahata¹, Lidiane Moura e Silva¹, Rodrigo Agra¹, Lisete Pontes¹, Larissa Montenegro¹, José Luciano Albuquerque¹ and Viviane Canadas¹

(1)
Division of Endocrinology, Hospital das Clínicas, Federal University of Pernambuco, Recife, Brazil

(2)
Pernambuco Center for Diabetes and Endocrinology, Federal University of Pernambuco, Recife, Brazil

(3)
Division of Endocrinology, Hospital Universitário de Brasilia, Brasilia, Brazil

(4)
Rua Clovis Silveira Barros, 84/1202, Boa Vista, Recife, CEP 50.050-270, Brazil

Published online: 27 November 2009

Abstract The expression of dopamine receptor subtypes has been reported in corticotroph adenomas, and this finding support the possibility for medical treatment of Cushing’s disease (CD) with dopamine agonists when conventional treatment has failed. The aim of this study was to evaluate the effectiveness of cabergoline (at doses of up 3 mg/week), alone or combined with relatively low doses of ketoconazole (up to 400 mg/day), in 12 patients with CD unsuccessfully treated by transsphenoidal surgery. After 6 months of cabergoline therapy, normalization of 24 h urinary free cortisol (UFC) levels occurred in three patients (25%) at doses ranging from 2–3 mg/week, whereas reductions ranging from 15.0 to 48.4% were found in the remaining. The addition of ketonocazole to the nine patients without an adequate response to cabergoline was able to normalize UFC excretion in six patients (66.7%) at doses of 200 mg/day (three patients), 300 mg/day (two patients) and 400 mg/day (one patient). In the remaining patients UFC levels did not normalize but a significant reduction ranging from to 44.4 to 51.7% was achieved. In two of the six responsive patients to combination therapy, the weekly dose of cabergoline could be later reduced from 3 to 2 mg. Our findings demonstrated that cabergoline monotherapy was able to reverse hypercortisolism in 25% of patients with CD unsuccessfully treated by surgery. Moreover, the addition of relatively low doses of ketoconazole led to normalization of UFC in about two-thirds of patients not achieving a full response to cabergoline.

Keywords Cushing’s disease - Cabergoline - Ketoconazole

---

Lucio Vilar
Email: lvilar@gmail.com

Fulltext Preview (Small, Large)

From http://www.springerlink.com/content/4m17t88p17424162/