Faster Adrenal Recovery May Predict Cushing’s Disease Recurrence

A shorter duration of adrenal insufficiency — when the adrenal gland is not working properly — after surgical removal of a pituitary tumor may predict recurrence in Cushing’s disease patients, a new study suggests.

The study, “Recovery of the adrenal function after pituitary surgery in patients with Cushing Disease: persistent remission or recurrence?,” was published in the journal Neuroendocrinology.

Cushing’s disease is a condition characterized by excess cortisol in circulation due to a tumor in the pituitary gland that produces too much of the adrenocorticotropic hormone (ACTH). This hormone acts on the adrenal glands, telling them to produce cortisol.

The first-line treatment for these patients is pituitary surgery to remove the tumor, but while success rates are high, most patients experience adrenal insufficiency and some will see their disease return.

Adrenal insufficiency happens when the adrenal glands cannot make enough cortisol — because the source of ACTH was suddenly removed — and may last from months to years. In these cases, patients require replacement hormone therapy until normal ACTH and cortisol production resumes.

However, the recovery of adrenal gland function may mean one of two things: either patients have their hypothalamus-pituitary-adrenal axis — a feedback loop that regulates ACTH and cortisol production — functioning normally, or their disease returned.

So, a team of researchers in Italy sought to compare the recovery of adrenal gland function in patients with a lasting remission to those whose disease recurred.

The study included 61 patients treated and followed at the Ospedale Maggiore Policlinico of Milan between 1990 and 2017. Patients had been followed for a median of six years (minimum three years) and 10 (16.3%) saw their disease return during follow-up.

Overall, the median time to recovery of adrenal function was 19 months, but while most patients in remission (67%) had not yet recovered their adrenal function after a median of six years, all patients whose disease recurred experienced adrenal recovery within 22 months.

Among those with disease recurrence, the interval from adrenal recovery to recurrence lasted a median of 1.1 years, but in one patient, signs of disease recurrence were not seen for 15.5 years.

Statistical analysis revealed that the time needed for adrenal recovery was negatively associated with disease recurrence, suggesting that patients with sorter adrenal insufficiency intervals were at an increased risk for recurrence.

“In conclusion, our study shows that the duration of adrenal insufficiency after pituitary surgery in patients with CD is significantly shorter in recurrent CD than in the persistent remission group,” researchers wrote.

“The duration of AI may be a useful predictor for CD [Cushing’s disease] recurrence and those patients who show a normal pituitary-adrenal axis within 2 years after surgery should be strictly monitored being more at risk of disease relapse,” they concluded.

From https://cushingsdiseasenews.com/2019/01/29/faster-adrenal-recovery-may-predict-recurrence-cushings-disease/

Transsphenoidal Surgery Leads to Remission in Children with Cushing’s Disease

Transsphenoidal surgery — a minimally invasive surgery for removing pituitary tumors in Cushing’s disease patients — is also effective in children and adolescents with the condition, leading to remission with a low rate of complications, a study reports.

The research, “Neurosurgical treatment of Cushing disease in pediatric patients: case series and review of literature,” was published in the journal Child’s Nervous System.

Transsphenoidal (through the nose) pituitary surgery is the main treatment option for children with Cushing’s disease. It allows the removal of pituitary adenomas without requiring long-term replacement therapy, but negative effects on growth and puberty have been reported.

In the study, a team from Turkey shared its findings on 10 children and adolescents (7 females) with the condition, who underwent microsurgery (TSMS) or endoscopic surgery (ETSS, which is less invasive) — the two types of transsphenoidal surgery.

At the time of surgery, the patients’ mean age was 14.8 years, and they had been experiencing symptoms for a mean average of 24.2 months. All but one had gained weight, with a mean body mass index of 29.97.

Their symptoms included excessive body hair, high blood pressure, stretch marks, headaches, acne, “moon face,” and the absence of menstruation.

The patients were diagnosed with Cushing’s after their plasma cortisol levels were measured, and there was a lack of cortical level suppression after they took a low-dose suppression treatment. Measurements of their adrenocorticotropic (ACTH) hormone levels then revealed the cause of their disease was likely pituitary tumors.

Magnetic resonance imaging (MRI) scans, however, only enabled tumor localization in seven patients: three with a microadenoma (a tumor smaller than 10 millimeters), and four showed a macroadenoma.

CD diagnosis was confirmed by surgery and the presence of characteristic pituitary changes. The three patients with no sign of adenoma on their MRIs showed evidence of ACTH-containing adenomas on tissue evaluation.

Eight patients underwent TSMS, and 2 patients had ETSS, with no surgical complications. The patients were considered in remission if they showed clinical adrenal insufficiency and serum cortisol levels under 2.5 μg/dl 48 hours after surgery, or a cortisol level lower than 1.8 μg/dl with a low-dose dexamethasone suppression test at three months post-surgery. Restoration of normal plasma cortisol variation, eased symptoms, and no sign of adenoma in MRI were also requirements for remission.

Eight patients (80%) achieved remission, 4 of them after TSMS. Two patients underwent additional TSMS for remission. Also, 1 patient had ETSS twice after TSMS to gain remission, while another met the criteria after the first endoscopic surgery.

The data further showed that clinical recovery and normalized biochemical parameters were achieved after the initial operation in 5 patients (50%). Three patients (30%) were considered cured after additional operations.

The mean cortisol level decreased to 8.71 μg/dl post-surgery from 23.435 μg/dl pre-surgery. All patients were regularly evaluated in an outpatient clinic, with a mean follow-up period of 11 years.

Two patients showed pituitary insufficiency. Also, 2 had persistent hypocortisolism — too little cortisol — one of whom also had diabetes insipidus, a disorder that causes an imbalance of water in the body. Radiotherapy was not considered in any case.

“Transsphenoidal surgery remains the mainstay therapy for CD [Cushing’s disease] in pediatric patients as well as adults,” the scientists wrote. “It is an effective treatment option with low rate of complications.”

 

From https://cushingsdiseasenews.com/2019/01/15/transsphenoidal-surgery-enables-cushings-disease-remission-pediatric-patients-study/

Vision Loss The First Sign Of Adrenal Tumour In 42-Year-Old Patient

A 42-year-old woman who presented to hospital with acute vision loss in her right eye was diagnosed with a benign tumour in her adrenal gland.

Writing in BMJ Case Reports, clinicians described how the patient presented with a visual acuity of 6/36 in her right eye and 6/6 in her left eye.

Investigations revealed an exudative retinal detachment in her right eye as well as a pigment epithelial detachment.

The patient had multifocal central serous retinopathy in both eyes.

The woman, who had hypertension and diabetes, was diagnosed with Cushing syndrome and a right adrenal adenoma was also discovered.

During a treatment period that spanned several years, the patient received an adrenalectomy followed by a maintenance dose of steroids.

The patient subsequently developed central serous retinopathy again which the clinicians believe might be related to steroid use.

The authors advised “careful deliberation” in prescribing a maintenance dose of steroids following removal of the adrenal glands because of the potential link to retinopathy.

From https://www.aop.org.uk/ot/science-and-vision/research/2018/12/17/vision-loss-the-first-sign-of-adrenal-tumour-in-42-year-old-patient

Neurosurgical treatment of Cushing disease in pediatric patients: case series and review of literature

 2018 Nov 28. doi: 10.1007/s00381-018-4013-5. [Epub ahead of print]

Abstract

AIM:

Pituitary adenomas are rare in childhood in contrast with adults. Adrenocorticotropic hormone (ACTH)-secreting adenomas account for Cushing’s disease (CD) which is the most common form of ACTH-dependent Cushing’s syndrome (CS). Treatment strategies are generally based on data of adult CD patients, although some difficulties and differences exist in pediatric patients. The aim of this study is to share our experience of 10 children and adolescents with CD.

PATIENTS AND METHOD:

Medical records, images, and operative notes of 10 consecutive children and adolescents who underwent transsphenoidal surgery for CD between 1999 and 2014 in Cerrahpasa Faculty of Medicine were retrospectively reviewed. Mean age at operation was 14.8 ± 4.2 years (range 5-18). The mean length of symptoms was 24.2 months. The mean follow-up period was 11 years (range 4 to 19 years).

RESULTS:

Mean preoperative cortisol level was 23.435 μg/dl (range 8.81-59.8 μg/dl). Mean preoperative ACTH level was 57.358 μg/dl (range 28.9-139.9 μg/dl). MR images localized microadenoma in three patients (30%), macroadenoma in four patients (40%) in our series. Transsphenoidal microsurgery and endoscopic transsphenoidal surgery were performed in 8 and 2 patients respectively. Remission was provided in 8 patients (80%). Five patients (50%) met remission criteria after initial operations. Three patients (30%) underwent additional operations to meet remission criteria.

CONCLUSION:

Transsphenoidal surgery remains the mainstay therapy for CD in pediatric patients as well as adults. It is an effective treatment option with low rate of complications. Both endoscopic and microscopic approaches provide safe access to sella and satisfactory surgical results.

KEYWORDS:

Cushing’s disease; Endoscopic pituitary surgery; Pediatric; Transsphenoidal microsurgery

PMID:
30488233
DOI:
10.1007/s00381-018-4013-5

Full Text

No Association Between Long-Term Gh Replacement, Comorbidities In Nonfunctioning Pituitary Adenoma

Hammarstrand C, et al. Eur J Endocrinol. 2018;doi:10.1530/EJE-18-0370.

Patients with growth hormone deficiency due to nonfunctioning pituitary adenoma experienced excessive morbidity due to cerebral infarction and sepsis regardless of whether they received long-term GH therapy, whereas treatment was associated with a normal incidence of type 2 diabetes, despite higher BMI and more severe hypopituitarism in treated patients, according to findings from an observational, registry-based study.

“Although growth hormone replacement therapy is well-established and reverses most of the features associated with GH [deficiency], one of the safety concerns is the reduction in insulin sensitivity and the potential risk of developing type 2 diabetes mellitus,” Daniel S. Olsson, MSc, MD, PhD, professor at the Sahlgrenska Academy Institute of Medicine at the University of Gothenburg, Sweden, and colleagues wrote in the study background.

Studies examining whether there is an association have produced mixed results, the researchers wrote, and it remains unknown to what extent GH deficiency — and GH therapy —contribute to the development of type 2 diabetes and other comorbidities, including cerebral infarction, malignant tumors, myocardial infarction or fractures.

Olsson and colleagues analyzed data from 426 patients treated or followed for nonfunctioning pituitary adenoma between 1997 and 2011, selected from the Swedish National Patient Register. Researchers assessed information on tumor treatment, hormone therapy, antihypertensive medication, BMI and duration of GH therapy. For patients with type 2 diabetes, researchers assessed HbA1c values, insulin treatment, oral antidiabetes therapies and lipid-lowering therapies. Researchers followed the cohort through December 2014 or until death. Patients were stratified by use of GH therapy. Researchers calculated standardized incidence ratios (SIRs) based on the observed number of comorbidities among patients with nonfunctioning pituitary adenoma vs. the expected number of comorbidities in the background population.

Within the cohort, 207 patients received GH therapy (145 men) and 219 did not (129 men). Median duration of GH therapy was 11.7 years; mean age at diagnosis was 56 years for treated patients and 65 years for untreated patients. Median follow-up time for treated and untreated patients was 12.2 years and 8.2 years, respectively.

Incidence of cerebral infarction was increased for the whole cohort regardless of GH therapy status, with an SIR of 1.39 (95% CI, 1.03-1.84), and was most evident among 97 patients who underwent radiotherapy, in which 19 cerebral infarctions occurred vs. the expected number of 9.8 (P = .011).

“The study showed an increased overall incidence of cerebral infarction in patients with [nonfunctioning pituitary adenoma] compared to the general population that was related to previous radiotherapy, but not to GH [replacement therapy],” the researchers wrote.

Incidence of myocardial infarction was similar for treated and untreated patients, with SIRs of 1.18 (95% CI, 0.73-1.8) and 1.23 (95% CI, 0.82-1.78), respectively. Incidence of receiving medical treatment for hypertension was also similar between groups.

In assessing incidence of type 2 diabetes, the researchers found that the SIR was higher among untreated patients (1.65; 95% CI, 1.06-2.46) vs. treated patients, who had an SIR similar to the background population (0.99; 95% CI, 0.55-1.63). Treated patients with type 2 diabetes had higher BMI vs. untreated patients with type 2 diabetes (P = .01), according to researchers, and glycemic status was similar among treated and untreated patients.

The incidence of sepsis requiring hospitalization was also similar between treated and untreated patients, with rates for both groups close to double that of the background population (P < .001). Incidence of malignant tumors was not increased for treated or untreated patients when compared against the background population, according to the researchers. – by Regina Schaffer

DisclosuresThe Gothenburg Growth Hormone Database is supported partly through unrestricted grants from Novo Nordisk, Pfizer and Sandoz. Olsson reports he has served as a consultant for Ipsen, Pfizer and Sandoz. Another author reports he has served as a consultant to AstraZeneca and Viropharma/Shire, and received lecture fees from Novo Nordisk, Otsuka and Pfizer.

From https://www.healio.com/endocrinology/neuroendocrinology/news/in-the-journals/%7B0739a3a3-f592-4352-93f0-2ee5b5a89251%7D/no-association-between-long-term-gh-replacement-comorbidities-in-nonfunctioning-pituitary-adenoma

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