A retrospective analysis of postoperative hypokalemia in pituitary adenomas after transsphenoidal surgery

Posted on May 23, 2017 by MaryO

Abstract.

Background

Pituitary adenoma is one of the most common intracranial neoplasms, and its primary treatment is endoscopic endonasal transsphenoidal tumorectomy. Postoperative hypokalemia in these patients is a common complication, and is associated with morbidity and mortality. This study aimed to analyze the etiopathology of postoperative hypokalemia in pituitary adenomas after endoscopic transsphenoidal surgery.

Methods and Materials

This retrospective study included 181 pituitary adenomas confirmed by histopathology. Unconditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Repeated measures ANOVA was used to analyze change in serum potassium levels at different time points.

Results

Multiple Logistic regression analysis revealed that only ACTH-pituitary adenoma (OR = 4.92, 95% CI [1.18–20.48], P = 0.029) had a significant association with postoperative hypokalemia. Moreover, the overall mean serum potassium concentration was significantly lower in the ACTH versus the non-ACTH group (3.34 mmol/L vs. 3.79 mmol/L, P = 0.001). Postoperative hypokalemia was predominantly found in patients with ACTH-pituitary adenoma (P = 0.033).

Conclusions

ACTH-pituitary adenomas may be an independent factor related postoperative hypokalemia in patients despite conventional potassium supplementation in the immediate postoperative period.

Cite this as

You L, Li W, Chen T, Tang D, You J, Zhang X. (2017) A retrospective analysis of postoperative hypokalemia in pituitary adenomas after transsphenoidal surgery. PeerJ5:e3337 https://doi.org/10.7717/peerj.3337

Read the entire article at https://peerj.com/articles/3337/

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Identification Of Potential Markers For Cushing’s Disease

Posted on January 21, 2016 by MaryO

Endocr Pract. 2016 Jan 20. [Epub ahead of print]

Broder MS1, Chang E1, Cherepanov D1, Neary MP2, Ludlam WH2.

Author information

Abstract

OBJECTIVE:

Cushing’s disease (CD) causes a wide variety of nonspecific symptoms, which may result in delayed diagnosis. It may be possible to uncover unusual combinations of otherwise common symptoms using ICD-9-CM codes. Our aim was to identify and evaluate dyads of clinical symptoms or conditions associated with CD.

METHODS:

We conducted a matched case-control study using a commercial healthcare insurance claims database, designed to compare the relative risk (RR) of individual conditions and dyad combinations of conditions among patients with CD versus matched non-CD controls.

RESULTS:

With expert endocrinologist input, we isolated 10 key conditions (localized adiposity, hirsutism, facial plethora, polycystic ovary syndrome, abnormal weight gain, hypokalemia, deep venous thrombosis, muscle weakness, female balding, osteoporosis) with RR varying from 5.1 for osteoporosis to 27.8 for hirsutism. The RR of dyads of these conditions ranged from 4.1 for psychiatric disorders/serious infections to 128.0 for hirsutism/fatigue in patients with vs. without CD. Construction of uncommon dyads resulted in further increases in RR beyond single condition analyses, such as osteoporosis alone had RR of 5.3, which increased to 8.3 with serious infections and to 52.0 with obesity.

CONCLUSION:

This study demonstrated that RR of any one of 10 key conditions selected by expert opinion was ≥5 times greater in CD compared to non-CD, and nearly all dyads had RR≥5. An uncommon dyad of osteoporosis and obesity had an RR of 52.0. If clinicians consider the diagnosis of CD when the highest-risk conditions are seen, identification of this rare disease may improve.

KEYWORDS:

Cushing’s disease; delay in diagnosis; disease markers; insurance claims; relative risk

PMID:
26789346
[PubMed – as supplied by publisher]

From http://www.ncbi.nlm.nih.gov/pubmed/26789346

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Higher Doses of ‘Abortion Pill’ Safe in Cushing’s?

Posted on May 16, 2014 by MaryO
By Kristina Fiore, Staff Writer, MedPage Today
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

LAS VEGAS — Higher doses of mifepristone for Cushing’s disease (Korlym) weren’t associated with increases in serious adverse events, researchers reported here.

Korlym is a glucocorticoid receptor antagonist better known as RU-486, or the “abortion pill.” It was approved for treating hyperglycemia associated with Cushing’s disease in 2012.

In an analysis of data from the SEISMIC trial, Dat Nguyen, MD, and colleagues found that similar percentages of patients had serious adverse events across all doses of the drug, reported.

They also reported at the American Association of Clinical Endocrinologists meeting here, that the proportion of the four most common adverse events — headache, fatigue, nausea, and hypokalemia — fell off after 10 weeks of the 24-week trial.

“Recent prescription data indicate that many physicians are not titrating beyond 300 mg per day, potentially limiting patients’ clinical response,” the researchers said.

The 2012 approval was based on the SEISMIC study, which followed 50 Cushing’s disease patients over 24-weeks in an open-label format. It found that daily doses improved blood sugar control and reduced insulin requirements.

Clinicians participating in the trial were told they could titrate beyond the starting dose of 300 mg a day. To look at the relationship between dose and safety, as well as response, Nguyen and colleagues looked at data on 40 of the patients who responded to therapy.

Most of them (90%) were taking at least 600 mg a day, 68% were taking at least 900 mg per day, and 44% took 1,200 mg daily.

Most of the responders (85%) had their initial clinical response at a dose of at least 600 mg daily.

Overall, there were 26 serious adverse events:

  • 10 at the 300 mg dose
  • 8 at the 600 mg dose
  • 3 at the 900 mg dose
  • 3 at the 1200 mg dose
  • 2 while off drug

 

When the researchers adjusted for the number of patients who had ever reached a given dose, the frequency of serious adverse events was similar across doses:

  • 10% of patients at 300 mg
  • 16% of patients at 600 mg
  • 15% of patients at 900 mg
  • 14% of patients at 1200 mg

 

The four most common adverse events decreased after week 10 – although that tracked an increase in dose (mean 588 mg/day before week 10 versus 895 mg/day thereafter).

Nguyen and colleagues concluded that higher doses of mifepristone weren’t associated with increases in serious adverse events or in the most common adverse events – and that better response was seen with higher doses.

Korlym was developed by Corcept Therapeutics of Menlo Park, Calif., as an orphan drug given that it is is believed only 5,000 patients are eligible for treatment. That gave the company 7 years of exclusive rights to market the agent for Cushing’s disease.

The label limits the drug’s indication to patients with endogenous Cushing’s disease who have type 2 diabetes or glucose intolerance and aren’t candidates for surgery, or failed to respond to surgical intervention.

The drug doesn’t reduce cortisol production but prevents it from binding to its receptor – an action separate from its blockade of the progesterone receptor, which makes it an effective agent in abortion.

Since the daily doses are in the same range as those used to induce abortion, the drug is contraindicated in pregnant women. It also carries a boxed warning that the drug will terminate a pregnancy.

From http://www.medpagetoday.com/MeetingCoverage/AACE/45790

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Pituitary tumor size not definitive for Cushing’s

Posted on July 12, 2013 by MaryO

By: SHERRY BOSCHERT, Family Practice News Digital Network

SAN FRANCISCO – The size of a pituitary tumor on magnetic resonance imaging in a patient with ACTH-dependent Cushing’s syndrome can’t differentiate between etiologies, but combining that information with biochemical test results could help avoid costly and difficult inferior petrosal sinus sampling in some patients, a study of 131 cases suggests.

If MRI shows a pituitary tumor larger than 6 mm in size, the finding is 40% sensitive and 96% specific for a diagnosis of Cushing’s disease as the cause of adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome, and additional information from biochemical testing may help further differentiate this from ectopic ACTH secretion, Dr. Divya Yogi-Morren and her associates reported at the Endocrine Society’s Annual Meeting.

Pituitary tumors were seen on MRI in 6 of 26 patients with ectopic ACTH secretion (23%) and 73 of 105 patients with Cushing’s disease (69%), with mean measurements of 4.5 mm in the ectopic ACTH secretion group and 8 mm in the Cushing’s disease group. All but one tumor in the ectopic ACTH secretion group were 6 mm or smaller in diameter, but one was 14 mm.

Because pituitary “incidentalomas” as large as 14 mm can be seen in patients with ectopic ACTH secretion, the presence of a pituitary tumor can’t definitively discriminate between ectopic ACTH secretion and Cushing’s disease, said Dr. Yogi-Morren, a fellow at the Cleveland Clinic.

That finding contradicts part of a 2003 consensus statement that said the presence of a focal pituitary lesion larger than 6 mm on MRI could provide a definitive diagnosis of Cushing’s disease, with no further evaluation needed in patients who have a classic clinical presentation and dynamic biochemical testing results that are compatible with a pituitary etiology (J. Clin. Endocrinol. Metab. 2003;88:5593-602). The 6-mm cutoff, said Dr. Yogi-Morren, came from an earlier study reporting that 10% of 100 normal, healthy adults had focal pituitary abnormalities on MRI ranging from 3 to 6 mm in diameter that were consistent with a diagnosis of asymptomatic pituitary adenomas (Ann. Intern. Med. 1994;120:817-20).

A traditional workup of a patient with ACTH-dependent Cushing’s syndrome might include a clinical history, biochemical testing, neuroimaging, and an inferior petrosal sinus sampling (IPSS). Biochemical testing typically includes tests for hypokalemia, measurement of cortisol and ACTH levels, a high-dose dexamethasone suppression test, and a corticotropin-releasing hormone (CRH) stimulation test. Although IPSS is the gold standard for differentiating between the two etiologies, it is expensive and technically difficult, especially in institutions that don’t regularly do the procedure, so it would be desirable to avoid IPSS if it’s not needed in a subset of patients, Dr. Yogi-Morren said.

The investigators reviewed charts from two centers (the Cleveland Clinic and the M.D. Anderson Cancer Center, Houston) for patients with ACTH-dependent Cushing’s syndrome seen during 2000-2012.

ACTH levels were significantly different between groups, averaging 162 pg/mL (range, 58-671 pg/mL) in patients with ectopic ACTH secretion, compared with a mean 71 pg/mL in patients with Cushing’s disease (range, 16-209 pg/mL), she reported. Although there was some overlap between groups in the range of ACTH levels, all patients with an ACTH level higher than 210 pg/mL had ectopic ACTH secretion.

Median serum potassium levels at baseline were 2.9 mmol/L in the ectopic ACTH secretion group and 3.8 mmol/L in the Cushing’s disease group, a significant difference. Again, there was some overlap between groups in the range of potassium levels, but all patients with a baseline potassium level lower than 2.7 mmol/L had ectopic ACTH secretion, she said.

Among patients who underwent a high-dose dexamethasone suppression test, cortisol levels decreased by less than 50% in 88% of patients with ectopic ACTH secretion and in 26% of patients with Cushing’s disease.

Most patients did not undergo a standardized, formal CRH stimulation test, so investigators extracted the ACTH response to CRH in peripheral plasma during the IPSS test. As expected, they found a significantly higher percent increase in ACTH in response to CRH during IPSS in the Cushing’s disease group, ranging up to more than a 1,000% increase. In the ectopic ACTH secretion group, 40% of patients did have an ACTH increase greater than 50%, ranging as high as a 200%-300% increase in ACTH in a couple of patients.

“Although there was some overlap in the biochemical testing, it is possible that it provides some additional proof to differentiate between ectopic ACTH secretion and Cushing’s disease,” Dr. Yogi-Morren said.

In the ectopic ACTH secretion group, the source of the secretion remained occult in seven patients. The most common identifiable cause was a bronchial carcinoid tumor, in six patients. Three patients each had small cell lung cancer, a thymic carcinoid tumor, or a pancreatic neuroendocrine tumor. One patient each had a bladder neuroendocrine tumor, ovarian endometrioid cancer, medullary thyroid cancer, or a metastatic neuroendocrine tumor from an unknown primary cancer.

The ectopic ACTH secretion group had a median age of 41 years and was 63% female. The Cushing’s disease group had a median age of 46 years and was 76% female.

Dr. Yogi-Morren reported having no financial disclosures.

sboschert@frontlinemedcom.com

On Twitter @sherryboschert

From Famiiy Practice News

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