Preoperative medical treatment in Cushing’s syndrome.

Posted on February 14, 2018 by MaryO

European Journal of Endocrinology — | February 14, 2018

Valassi E, et al. – This study was performed to assess how frequently preoperative medical treatment (PMT) was given to Cushing’s syndrome (CS) patients across Europe and to investigate differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery. In addition, the physicians determined if PMT influenced the postoperative outcome in pituitary-dependent CS (PIT-CS). In contrast with adrenal-dependent CS (ADR-CS), CS from an ectopic source (ECT-CS) and PIT-CS exhibited greater likelihood of receiving PMT. Data reported more severe clinical features at the diagnosis and poorer quality of life in PIT-CS patients treated with PMT. The interpretation of immediate postoperative outcome could be confounded with PMT. They recommended follow-up to definitely evaluate surgical results.

Methods

  • A total of 1,143 CS patients entered into the ERCUSYN database from 57 centres in 26 countries.
  • During this study, 69% patients presented with PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS), and 1% were classified as having CS from other causes (OTH-CS).

Results

  • In this study, 20% of patients took PMT.
  • PMT was offered more frequently in ECT-CS and PIT-CS compared to ADR-CS (p < 0.001).
  • Ketoconazole (62%), metyrapone (16%), and a combination of both (12%) were the most commonly used drugs.
  • The median (interquartile range) duration of PMT was 109 (98) days.
  • More severe clinical features at diagnosis and poorer quality of life were noted in PIT-CS patients treated with PMT compared to those undergoing primary surgery (SX) (p < 0.05).
  • PIT-CS patients treated with PMT were more likely to have normal cortisol (p < 0.01) and a lower remission rate (p < 0.01) within 7 days of surgery.
  • Between SX and PMT groups, no differences in morbidity or remission rates were observed within 6 months of surgery.

Read the full article on European Journal of Endocrinology

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Temozolomide May Partially Improve Aggressive Pituitary Tumors Causing Cushing’s Disease

Posted on February 10, 2018 by MaryO

The chemotherapy temozolomide partially improved a case of an aggressive pituitary tumor that caused symptoms of Cushing’s disease (CD), according to a new study in Poland. However, after tumor mass and cortisol levels were stabilized for a few months, the patient experienced rapid progression, suggesting that new methods for extending the effects of temozolomide are needed.

The study, “Temozolomide therapy for aggressive pituitary Crooke’s cells corticotropinoma causing Cushing’s Disease: A case report with literature review,” appeared in the journal Endokrynologia Polska.

Aggressive pituitary tumors are usually invasive macroadenomas, or benign tumors larger than 10 mm.

A very rare subset of pituitary adenoma — particularly corticotropinoma, or tumors with excessive secretion of corticotropin (ACTH) — exhibit Crooke’s cells. These tumors are highly invasive, have a high recurrence rate, and are often resistant to treatment.

Information is not widely available about the effectiveness of treating aggressive pituitary tumors, particularly those that cause Cushing’s disease. The management of these tumors usually requires neurosurgery, followed by radiotherapy, and pharmacotherapy. However, the chemotherapy medication temozolomide has been increasingly used as a first-line treatment after initial evidence of its effectiveness in treating glioblastoma, the most common form of brain cancer.

In this study, researchers at the Jagiellonian University, in Poland, discussed the case of a 61-year-old man with ACTH-dependent Cushing’s syndrome caused by Crooke’s cell corticotropinoma.

The patient first presented with symptoms of severe hypercorticoidism — the excessive secretion of steroid hormones from the adrenal cortex — in December 2011. He also showed advanced heart failure, severe headaches, and impaired vision, which had started two or three years before diagnosis. Examinations revealed osteoporosis and a fracture in the Th5 vertebra.

His morning ACTH levels were high. The same was observed for mean cortisol levels even after dexamethasone treatment, which was suggestive of a pituitary tumor secreting ACTH. MRIs showed the existence of a tumor mass, later identified as a macroadenoma with high cell polymorphism, the presence of Crooke’s cells, and ACTH secretion.

The patient was referred for transsphenoidal nonradical neurosurgery, performed through the nose and the sphenoid sinus, and bilateral adrenalectomy, or the surgical removal of the adrenal glands, in 2012-2013. However, he developed fast, postoperative recurrence of hypercorticoidism and tumor regrowth. This led to three additional transsphenoidal neurosurgeries and radiotherapy.

The patient’s clinical status worsened as he developed severe cardiac insufficiency. Doctors began temozolomide treatment in April 2015, which did not result in adverse effects throughout treatment.

The initial standard dose (150–200 mg/m2) was given once daily in the morning for five consecutive days, in a 28-day cycle. The patient also received 600 mg of ketoconazole, an antifungal medication. Ondansetron was administered to prevent nausea and vomiting.

Subsequent examinations revealed clinical and biochemical improvements, including a reduction in ACTH and cortisol levels. In addition, the patient also showed reduced cardiac insufficiency, less frequent and less severe headaches, visual field improvements, and better physical fitness and mood.

However, clinical symptoms worsened after the eighth temozolomide cycle. The tumor size also suddenly increased after the ninth cycle, reaching the inner ear. Temozolomide was then discontinued and ACTH levels increased by 28 percent one month later. The patient also demonstrated deteriorated vision, hearing loss, and strong headaches.

Clinicians then decided to start treatment with the Cushing’s disease therapy Signifor (pasireotide), but a worsening of diabetes was observed, and the patient died in February 2016.

“The most probable reason for death was compression of the brainstem, which had been observed in the last MRI of the pituitary,” the researchers wrote, adding that “due to the very short duration of treatment, any conclusions on the treatment with Signifor cannot be drawn.”

Overall, “the results of the presented case suggest that [temozolomide] treatment monotherapy could have only partial response in aggressive corticotroph adenoma causing Cushing’s disease, followed by sudden progression,” the investigators wrote. This contrasts with mostly responsive cases reported in research literature, they noted.

“Therefore, further research on the factors of responsiveness and on novel methods to extend the duration of the effect of [temozolomide] should be carried out,” they wrote.

From https://cushingsdiseasenews.com/2018/02/08/cushings-disease-case-study-poland-shows-temozolomide-temporarily-effective-treating-aggressive-pituitary-tumor/

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Pituitary Gland Resection May Help Manage Presumed Cushing’s Patients

Posted on December 16, 2017 by MaryO

 

The surgical removal of two-thirds of the pituitary gland is associated with high initial remission rates and low operative morbidity in patients with suspected Cushing’s disease, when no tumor is found on the gland during surgical exploration.

Cushing’s disease (CD) is caused by increased levels of glucocoticosteroids, such as adrenocorticotropic hormone (ACTH), circulating in the blood.

In nearly 70 percent of cases this happens as a result of benign tumors on the pituitary gland, which produce excess ACTH. In these patients, the most effective and first-line treatment is surgical removal of the pituitary gland tumor.

During the diagnostic stage, clinicians use several methods to identify and localize the source of excessive ACTH. But these methods can fail, and the presence of a tumor in the pituitary is not always confirmed. If the tumor remains unidentified during surgical exploration, it falls to the surgeon’s discretion about how to manage their patients.

Researchers at the University of Colorado Denver School of Medicine provided an overview of their experience on the management of patients with presumed Cushing’s disease who underwent surgical treatment.

The study, “Negative surgical exploration in patients with Cushing’s disease: benefit of two-thirds gland resection on remission rate and a review of the literature,” was published in the Journal of Neurosurgery.

“The diagnosis and treatment of CD is one of the most challenging entities that pituitary neurosurgeons, endocrinologists, and pathologists face,” the researchers wrote. “The ability to make a correct diagnosis and deliver a high likelihood of remission after surgery relies heavily on the performance of a meticulous workup and rational surgical strategy.”

The team retrospectively analyzed all cases that had been referred to the Department of Neurosurgery of CU School of Medicine between 1989 and 2011 for a potential ACTH-secreting pituitary tumor.

During this period, 161 cases of Cushing’s patients who underwent surgical tumor resection were reported. In 22 patients, the surgeon was unable to detect a tumor.

In these cases the surgical team decided to remove two-thirds of the gland, with resection of the lateral and inferior portions of the pituitary. All 22 patients were treated using a consistent technique performed by a single surgeon.

Posterior tissue analysis confirmed that six of these patients had pituitary ACTH-secreting tumors. In the remaining 16 patients, no tumor was identified. In three patients the team believed that overproduction of ACTH could be due to an overgrowth of ACTH-secreting cells rather than expansion.

The team believes that these findings underscore the difficulty of accurately diagnosing very small pituitary tumors pre- and post-operatively.

The 22 patients were followed for a mean time of 98.9 months, or 8.2 years. No remissions were observed in the six patients who had ACTH-secreting tumors or in 12 of the remaining patients. Blood analysis in follow-up exams confirmed these patients had normal levels of glucocoticosteroids.

Four patients continued to show persistent elevated amounts of ACTH. Additional clinical evaluations revealed that two patients had ACTH-secreting lung tumors, and one patient was suspected of having an ACTH-secreting tumor on a brain region close to the pituitary. There was one case where the clinical team was unable to identify the origin of elevated ACTH.

Only three patients required hormone replacement after the two-thirds gland removal to overcome a newly detected hormone deficit. The approach used by the surgical team was, overall, found to be safe with no severe side effects reported.

“Currently, when the neurosurgeon is faced with the inability to identify a discrete adenoma intraoperatively, there is little uniformity in the literature as to how to proceed,” the team wrote. “We believe this [pituitary resection] approach will be useful to help guide surgeons in the operative treatment of this particularly difficult group of patients.”

From https://cushingsdiseasenews.com/2017/12/14/pituitary-gland-resection-may-help-presumed-cushings-disease-patients/

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2 Health Conditions That Can Cause Hyperpigmentation

Posted on December 15, 2017 by MaryO

Addison’s disease: Hyperpigmentation is a classic symptom of Addison’s disease, an endocrine disorder in which the adrenal glands fails to produce steroid hormone. The disease causes darkening of the skin in certain areas.

Cushing’s syndrome: The abnormal amount of cortisol in the human body causes a condition known as the Cushing’s syndrome. And one of the symptoms of the disorder is hyperpigmentation of the skin.

Adapted from http://www.thehealthsite.com/diseases-conditions/health-conditions-that-can-cause-hyperpigmentation/

Filed under: adrenal, Cushing's, pituitary, symptoms | Tagged: , , , , , , | Leave a comment »

Patients Undergoing Adrenalectomy Should Receive Steroid Substitutive Therapy

Posted on December 14, 2017 by MaryO

All patients who undergo removal of one adrenal gland due to Cushing’s syndrome (CS) or adrenal incidentaloma (AI, adrenal tumors discovered incidentally) should receive a steroid substitutive therapy, a new study shows.

The study, “Predictability of hypoadrenalism occurrence and duration after adrenalectomy for ACTH‐independent hypercortisolism,” was published in the Journal of Endocrinological Investigation.

CS is a rare disease, but subclinical hypercortisolism, an asymptomatic condition characterized by mild cortisol excess, has a much higher prevalence. In fact, subclinical hypercortisolism, is present in up to 20 percent of patients with AI.

The hypothalamic-pituitary-adrenal axis (HPA axis) is composed of the hypothalamus, which releases corticotropin-releasing hormone (CRH) that acts on the pituitary to release adrenocorticotropic hormone (ACTH), that in turn acts on the adrenal gland to release cortisol.

To avoid excess cortisol production, high cortisol levels tell the hypothalamus and the pituitary to stop producing CRH and ACTH, respectively. Therefore, as CS and AI are characterized by high levels of cortisol, there is suppression of the HPA axis.

As the adrenal gland is responsible for the production of cortisol, patients might need steroid substitutive therapy after surgical removal of AI. Indeed, because of HPA axis suppression, some patients have low cortisol levels after such surgeries – clinically known as post-surgical hypocortisolism (PSH), which can be damaging to the patient.

While some researchers suggest that steroid replacement therapy should be given only to some patients, others recommend it should be given to all who undergo adrenalectomy (surgical removal of the adrenal gland).

Some studies have shown that the severity of hypercortisolism, as well as the degree of HPA axis suppression and treatment with ketoconazole pre-surgery in CS patients, are associated with a longer duration of PSH.

Until now, however, there have been only a few studies to guide in predicting the occurrence and duration of PSH. Therefore, researchers conducted a study to determine whether HPA axis activity, determined by levels of ACTH and cortisol, could predict the occurrence and duration of PSH in patients who undergo an adrenalectomy.

Researchers studied 80 patients who underwent adrenalectomy for either CS or AI. Prior to the surgery, researchers measured levels of ACTH, urinary free cortisol (UFC), and serum cortisol after 1 mg dexamethasone suppression test (1 mg-DST).

After the surgery, all patients were placed on steroid replacement therapy and PSH was determined after two months. For those with PSH, levels of cortisol were determined every six months for at least four years.

Results showed that PSH occurred in 82.4 percent of CS patients and 46 percent of AI patients. PSH lasted for longer than 18 months in 50 percent of CS and 30 percent of AI patients. Furthermore, it lasted longer than 36 months for 35.7 percent of CS patients.

In all patients, PSH was predicted by pre-surgery cortisol levels after the 1 mg-DST, but with less than 70 percent accuracy.

In AI patients, a shorter-than-12-month duration of PSH was not predicted by any HPA parameter, but was significantly predicted by an absence of pre-surgery diagnosis of subclinical hypercortisolism.

So, this study did not find any parameters that could significantly predict with high sensitivity and specificity the development or duration of PSH in all patients undergoing adrenalectomy.

Consequently, the authors concluded that “the PSH occurrence and its duration are hardly predictable before surgery. All patients undergoing unilateral adrenalectomy should receive a steroid substitutive therapy.”

From https://cushingsdiseasenews.com/2017/12/08/therapy-cushings-patients-adrenalectomy/

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