Mortality in adults with hypopituitarism

endo2016

 

April 04, 2016

Oral Session: Pituitary Patients and Outcomes

Mortality in adults with hypopituitarism: A systematic review and meta-analysis

S Jasim, F Alahdab, A Ahmed, S Tamhane, TB Nippoldt, H Murad

Summary: The purpose of this study was to review existing literature on mortality in hypopituitarism and determine possible predictors of this outcome to help create clinical practice guidelines. Premature mortality may be associated with hypopituitarism, and the risk of hypopituitarism is higher in women and patients diagnosed at a younger age, concluded researchers.

Methods:

  • Researchers conducted a comprehensive search of multiple databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus.
  • Using a predefined protocol, they selected eligible studies that evaluated patients with hypopituitarism and reported mortality estimates.
  • Reviewers, independently and in duplicate, extracted data and assessed the risk of bias.

Results:

  • A total of 12 studies (published 1996 to 2015) that reported on 23515 patients were included in this review.
  • Compared to the general population, hypopituitarism was associated with an overall excess mortality (weighted SMR of 1.52; 95% CI: 1.14- 2.04), P=0.000.
  • The following were independent risk factors for increased mortality: younger age at diagnosis, female gender, diagnosis of craniopharyngioma, radiation therapy, transcranial surgery, DI, and hypogonadism.

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZ6AA1CEC190F5428EA690616DAA054518/57001/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-ENDO2016&nonus=0

Cushing’s disease associated with USP8 mutations

endo2016

 

April 04, 2016

Oral Session: Pituitary Patients and Outcomes

Cushing’s disease associated with USP8 mutations

RR Correa, FR Faucz, A Angelousi, N Settas, P Chittiboina, MB Lodish, CA Stratakis

Summary: In Cushing’s disease (CD), pituitary corticotroph adenomas secrete excessive adrenocorticotropic hormone (ACTH), resulting in hypercortisolism. Often, the genetic pathogenesis of CD remains unknown, but recent studies have shown that the ubiquitin-specific protease 8 gene (USP8) is frequently mutated in CD. This gene codes for a protein deubiquitinase that inhibits the lysosomal degradation of the epidermal growth factor receptor. Researchers determined that pediatric patients with USP8 mutations were predominantly female and presented with higher ACTH levels than control patients.

Methods:

  • To further study the prevalence of mutations in USP8, researchers sequenced the complete USP8-coding and surrounding intronic regions in 97 patients with diagnosed CD by Sanger sequencing of germline DNA (n=97) and tumor DNA (n=50).
  • They analuzed biochemical and clinical characteristics in all the patients with predicted (by in silico analysis) damaging USP8 mutations and it was compared to patients without the mutation (control).

Results:

  • Overall researchers identified 18 (18.5%) patients with corticotroph adenomas who had USP8mutations, 13 with germline mutation, 2 with a germline and a new somatic mutation, and 5 with somatic mutation only.
  • All the somatic mutations that were not present at the germline level were mutations in the previously described hotspot.
  • Female-to-male ratio in the patients with USP8 mutations was 3.5:1 compared to the control ratio of 1:1 (P=0.05).
  • The mean age was 13 years old (range 6-18) and 72% (13/18) were whites.
  • Three of the mutant tumors were macroadenomas (≄ 1 cm) and 15 were microadenomas (< 1 cm).
  • In cases, mean basal plasma ACTH was 53.2±28.5 pg/mL and 39.6±19.1 pg/mL in the control group (P=0.02).
  • Researchers did not note any statistically significant differences in cortisol levels between the groups.

Day 5, Cushing’s Awareness Challenge 2016

In Day 9 on April 9, 2015, I wrote about how we got the Cushing’s colors of blue and yellow.  This post is going to be about the first Cushing’s ribbons.

 

I was on vacation  in September, 2001 when SuziQ called me to let me know that we had had our first Cushie casualty (that we knew about).

On the message boards, Lorrie wrote: Our dear friend, Janice died this past Tuesday, September 4, 2001. I received an IM from her best friend Janine, tonight. Janine had been reading the boards, as Janice had told her about this site, and she came upon my name and decided to IM me. I am grateful that she did. She said that she knew that Janice would want all of us to know that she didn’t just stop posting.

For all of the newcomers to the board that did not know Janice, she was a very caring individual. She always had something positive to say. Janice was 36 years old, was married and had no children. She had a miscarriage in December and began to have symptoms of Cushing’s during that pregnancy. After the pregnancy, she continued to have symptoms. When discussing this with her doctor, she was told that her symptoms were just related to her D&C. She did not buy this and continued until she received the accurate diagnosis of Cushing’s Syndrome (adrenal) in March of 2001. Tragically, Janice’s tumor was cancerous, a very rare form of Cushing’s.

Janice then had her tumor and adrenal gland removed by open adrenalectomy, a few months ago. She then began chemotherapy. She was very brave through this even though she experienced severe side effects, including weakness and dizziness. She continued to post on this board at times and even though she was going through so much, she continued with a positive attitude. She even gave me a referral to a doctor a few weeks ago. She was my inspiration. Whenever I thought I had it bad, I thought of what she was dealing with, and I gained more perspective.

Janice was having difficulty with low potassium levels and difficulty breathing. She was admitted to the hospital, a CT scan was done and showed tumor metastasis to the lungs. She then was begun on a more aggressive regimen of chemo. She was discharged and apparently seemed to be doing well.

The potassium then began to drop again, she spiked a temp and she was again admitted to the hospital. She improved and was set to be discharged and then she threw a blood clot into her lungs. She was required to be put on a ventilator. She apparently was at high risk for a heart attack. Her husband did not want her to suffer anymore and did not want her to suffer the pain of a heart attack and so chose for the doctors to discontinue the ventilator on Tuesday. She died shortly thereafter.

Janice was our friend. She was a Cushie sister. I will always remember her. Janine asked me to let her know when we get the Cushing’s ribbons made as she and the rest of Janice’s family would like to wear them in her memory. She said that Janice would want to do anything she could to make others more aware of Cushing’s.

The image at the top of the page shows the first blue and yellow ribbon which were worn at Janice’s funeral.  When we had our “official ribbons” made, we sent several to Janice’s family.

Janice was the first of us to die but there have been more, way too many more, over the years.  I’ll write a bit more about that on Day 21.

Decreased prefrontal functional brain response in women with Cushing’s syndrome in remission

endo2016

 

April 03, 2016

Poster Session: Cushing’s Syndrome and Primary Adrenal Disorders

Decreased prefrontal functional brain response in women with Cushing’s syndrome in remission

O Ragnarsson, A Stomby, P Dahlqvist, JA Evang, M Ryberg, T Olsson, J Bollerslev, L Nyberg, G Johannsson

Summary: Neuropsychiatric symptoms including impairment of memory, attention, and executive function are important features of Cushing’s syndrome (CS). Notably, patients with CS in remission commonly demonstrate residual cognitive dysfunction, which has been suggested to be linked to incomplete recovery of neuronal function. Researchers sought to assess whether functional brain responses are altered during cognitive testing in patients with CS in remission. During episodic memory, women with CS in long-term remission have reduced functional brain responses in the prefrontal cortex and in the hippocampus.

Methods:

  • Included in this study were 19 women previously treated for CS (14 Cushing’s disease and 5 cortisol producing adrenal adenomas) and 19 controls, matched for age, gender, and education.
  • The median (interquartile range) remission time was 7 (6-10) years.
  • Researchers studied brain activity with functional magnetic resonance imaging during an episodic-memory face-name task.
  • The primary regions of interest were the prefrontal cortex and the hippocampus.
  • A voxel wise comparison of functional brain responses in patients and controls was performed, and an uncorrected P < 0.001 was considered significant.

Results:

  • During memory encoding, patients displayed lower functional brain responses in the left and right prefrontal gyrus (Brodmann areas [BA] 44, 45, and 46) as well as the right inferior occipital gyrus (BA 18) compared to controls (P < 0.001 for all).
  • Patients displayed lower functional brain responses in several brain areas including the prefrontal, parietal, occipital, and cerebellar cortices bilaterally during memory retrieval.
  • The most predominant difference was found in the right prefrontal cortex (BA 46 and 48; P < 0.001).
  • Reduced functional response in left dorsolateral prefrontal cortex was seen for patients during both encoding and retrieval.
  • Researchers compared the functional brain responses in four hippocampal clusters that were significantly activated during memory encoding among all participants (P < 0.05, FDR).
  • Patients had a trend toward lower functional brain responses in the left anterior hippocampus compared to controls (P=0.05).

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZ6AA1CEC190F5428EA690616DAA054518/56991/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-ENDO2016&nonus=0

Cushing’s Syndrome and Primary Adrenal Disorders

endo2016

 

April 03, 2016

Oral Session: Cushing’s Syndrome and Primary Adrenal Disorders

Patients with diabetes mellitus diagnosed with Addison’s disease have a markedly increased additional risk of death

D Chantzichristos, A Persson, B Eliasson, M Miftaraj, S Franzén, R Bergthorsdottir, S Gudbjörnsdottir, A-M Svensson, G Johannsson

Summary: Researchers sought to determine if patients with diabetes (DM) who are diagnosed with Addison’s disease (AD) have an increased risk of mortality (DM+AD). They concluded that patients diagnosed with DM+AD had a nearly 4-fold increased risk of mortality compared to controls.

Methods:

  • Researchers identified patients who were first diagnosed with DM (type 1 or 2) and then AD using both the Swedish National Diabetes Register (NDR) and the National Inpatient Register between January 1st, 1996 and December 31th, 2012.
  • Each patients was matched with 5 controls based on sex, year of birth, type of DM, year when DM was diagnosed, and period of time in NDR were selected in NDR.
  • Researchers obtained causes of death data for both groups during the same time period from the Swedish Register for Cause-Specific Mortality.

Results:

  • A total of 1,355 patients were identified: 226 patients had DM (type 1 or 2) and AD and 1,129 matched DM controls.
  • At baseline, patients with DM+AD and patients with DM had a mean (±SD) age of 52.3 (±20.1) and 54.1 (±18.9) years, respectively.
  • In both groups, 47% were women and 65% had type 1 DM.
  • Mean (±SD) HbA1c at baseline was 7.8% (±3.5%) or 62.0 (±14.7) mmol/mol for the DM+AD group and 7.6% (±3.5%) or 59.6 (±14.7) mmol/mol for the DM controls.
  •  More than one-quarter of patients with DM+AD (64/226, 28%) died vs 112 of 1,129 controls (10%).
  • The estimated relative risk increase (hazard ratio) in overall mortality in the DM+AD group was 3.83 (95% confidence interval, 2.80 to 5.24) compared with the DM controls.
  • There was no significant association between type of DM and gender on relative mortality risk.
  • The most common cause of death in both groups was cardiovascular diseases (33% and 34%, respectively).
  • The second most common cause of death in DM+AD patients was DM and its related complications (23%) and cancer in the DM group (29%).
  • Fourteen percent of DM+AD patients died from cancer.

From http://www.mdlinx.com/endocrinology/conference-abstract.cfm/ZZ6AA1CEC190F5428EA690616DAA054518/56981/?utm_source=confcoveragenl&utm_medium=newsletter&utm_content=abstract-list&utm_campaign=abstract-ENDO2016&nonus=0

%d bloggers like this: