Interview with a Doctor on Trans-Sphenoidal surgery

Posted on August 3, 2016 by MaryO

Dr. Julius July: Neurosurgeon at the Neuroscience Center of Siloam Hospitals Lippo Village Karawaci 

A SIMPLE AND QUICK WAY TO REMOVE TUMORS VIA SURGERY THROUGH THE NOSTRIL

The mention of the word “surgery” evokes images of lengthy and elaborate procedures that involve delicate acts of cutting, abrading or suturing different parts of the body to treat an injury or disease.

This widely-held perception has led some to develop an irrational fear of surgery–especially if an operation involves a critical organ, such as the heart, or in the case of trans-sphenoidal surgery, a procedure used to remove tumors from the hormone-regulating pituitary gland located at the base of the brain.

Though the procedure has been around in different forms for the past three decades, individuals who may be in dire need of it might fear or avoid it.

To demystify this specific method of surgery, J+ spoke with Julius July, a neurosurgeon at the Neuroscience Center of Siloam Hospitals Lippo Village Karawaci. He has performed hundreds of trans-sphenoidal operations on patients throughout the country since 2008. Below is our interview, edited for length and clarity.

Tell us more about trans-sphenoidal surgery.

The goal is to extract benign tumors of the pituitary gland that are called pituitary adenoma. The pituitary gland controls different secretions of hormones. If there is a tumor and it grows large, one of the consequences could be that a patient goes blind. It can also lead to symptoms manifesting in other parts of the body due to excess hormone production, depending on the type of hormone affected by the tumor.

What does a neurosurgeon do during the procedure?

As neurosurgeons we use an endoscope with a camera attached to it and insert the instrument through the nostril. We go through the right nostril and through the sinus to reach the tumor and remove it. Once that is done, we add a coagulant to prevent bleeding. The operation takes only an hour to 90 minutes to perform and is minimally invasive. People come in and expect the surgery to last five or six hours. They hear “surgery” and fearfully assume that. But modern trans-sphenoidal surgery is simple, only lasting one to two hours.

What’s the prognosis after surgery?

In 80 percent of cases, all it takes is one surgery to remove a tumor. However, some need repeated intervention, while others require radiation. Some tumors want to invade their surroundings. In these cases, the surrounding area is a blood vessel. We can’t totally remove that type of tumor. But such cases are rare. If a patient needs more than two operations, we usually recommend radiation, because who wants to have a lot of operations?

What are the symptoms of pituitary adenoma?

Symptoms depend on whether a tumor affects hormone production or the optic nerve. The principal complaints are related to a patient’s field of vision becoming narrower. If there is a tumor in the pituitary gland area, the eye can’t see too widely. The tumors would press on the optic nerve, which leads to the periphery of your vision getting blurry.

If the tumor affects hormone production, the symptoms depend on the specific type of hormone that the tumor has affected. Different hormones have different roles. Excess prolactin hormones can lead to women–or even men–producing breast milk. If a woman who isn’t pregnant is producing breast milk, they need to be checked. The basic ingredient of milk is calcium. Without treatment, the woman will have porous bone problems. It also leads to reduced libido. If men have an excess of these prolactin hormones, they cannot get erections and will become impotent.

How does these problem develop in the first place?

Mutations lead to the creation of these benign tumors. Some things make mutations easier, such as smoking or exposure to radiation or specific chemicals. It could be anything. You could have eaten tofu and it had formalin or some meatballs with borax. Preventing it obviously requires a healthy lifestyle, but that’s easier said than done.

It’s not just one thing that causes these tumors.

Who does this pituitary tumor affect?

It affects both genders equally, more or less. The risk of pituitary adenoma compared to all other types of brain tumors is 15 percent. Children are also affected, though the condition is statistically much more likely to afflict adults. Of my patients, two in 70 would be children.

How is it diagnosed?

The doctor will check your hormones after a blood test and identify the problem. For example, if the condition affects growth hormones, a person can grow to two meters or more in height, which leads to gigantism. Alternatively, a condition could lead to horizontal growth–a bigger tongue, bigger fingers and changing shoes each month. The tongue can become so big that it causes breathing problems. Growth hormone overproduction is like a factory with the machine working overtime. As a result, a person’s life span can get cut in half. The heart works overtime, they keep growing and they die prematurely.

How many operations do you perform a year?

I’ve been doing these operations since 2008. I handle 60 to 70 such surgeries a year.

Any notable success stories to share?

One patient from Central Java came in blind. I examined him and said that there was no way we could save his vision by removing his tumor. He was crying. He had been blind for a week. But if no action was taken, the tumor would keep growing and would lead him to becoming crippled. At the end, he decided that he still wanted the operation. Surprisingly though, after the operation, he was able to see. Three months later, he was driving and reading newspapers. It was a fascinating case.

From http://www.thejakartapost.com/news/2016/07/30/well-being-trans-sphenoidal-surgery.html

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GH therapy increases fracture risk in patients previously treated for acromegaly

Posted on July 16, 2016 by MaryO

van Varsseveld NC, et al. Pituitary. 2016;doi:10.1007/s11102-016-0716-3.

Adult patients with severe growth hormone deficiency previously treated for acromegaly saw an increased fracture risk after 6 years of growth hormone replacement therapy, whereas those previously treated for Cushing’s disease did not experience the same risk, according to a recent observational study.

Nadege C. van Varsseveld, MD, of the department of internal medicine at VU University Medical Center in Amsterdam, and colleagues analyzed data from 1,028 patients with previous nonfunctioning pituitary adenoma (NFPA; n = 783), acromegaly (n = 65) and Cushing’s disease (n = 180), identified through the Dutch National Registry of Growth Hormone Treatment in Adults, a nationwide, long-term surveillance study in patients with severe GH deficiency. Data were collected biannually from medical records through 2009. Baseline DXA measurements were available for 414 patients; 71 (17.1%) had osteoporosis at one or more of the measured sites; 147 (35.5%) had osteopenia.

During a mean follow-up of 5.2 years, researchers found that 166 of patients with previous NFPA were prescribed osteoporosis medications (21.3%), as were 69 patients with previous Cushing’s disease (38.5%) and 22 patients with previous acromegaly (33.4%). During follow-up, 39 patients experienced fractures (3.8%; 32 experiencing one fracture), including 26 patients in the previous NFPA group, eight patients in the previous Cushing’s disease group and five patients in the previous acromegaly group. The median time between baseline and first fracture was 2.4 years (mean age, 59 years).

Researchers found that fracture risk did not differ between groups before 6 years’ follow-up. Fracture risk increased in patients with previous acromegaly after 6 years’ follow-up, but not for those with previous Cushing’s disease vs. patients with NFPA. Results persisted after adjustment for multiple factors, including sex, age, fracture history and the extent of pituitary insufficiency.

The researchers noted that patients with previous Cushing’s disease were younger and more often women and had a greater history of osteopenia or osteoporosis, whereas patients with acromegaly had a longer duration between tumor treatment and the start of GH therapy and were treated more often with radiotherapy.

“During active acromegaly, increased bone turnover has been observed, but reported effects on [bone mineral density] are heterogeneous,” the researchers wrote. “It is postulated that cortical BMD increases, whereas trabecular BMD decreases or remains unaffected.

“The increased fracture risk in the present study may be a long-term effect of impaired skeletal health due to previous GH excess, even though this was not reflected by an increased occurrence of osteopenia or osteoporosis in the medical history,” the researchers wrote. – by Regina Schaffer

Disclosure: One researcher reports receiving consultancy fees from Novartis and Pfizer.

From http://www.healio.com/endocrinology/hormone-therapy/news/online/%7B92a67ad7-3bd5-46f0-b999-0a8e3486edab%7D/gh-therapy-increases-fracture-risk-in-patients-previously-treated-for-acromegaly

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Elevated late-night salivary cortisol may indicate recurrent Cushing’s disease

Posted on July 15, 2016 by MaryO

Carroll TB, et al. Endocr Pract. 2016;doi:10.4158/EP161380.OR.

 

Elevated late-night salivary cortisol may serve as an early biochemical marker of recurrent Cushing’s disease, and prompt intervention may result in clinical benefits for people with Cushing’s disease, according to recent study findings.

According to the researchers, late-night salivary cortisol level is more sensitive for detecting Cushing’s disease recurrence compared with urinary free cortisol or a dexamethasone suppression test.

Ty B. Carroll, MD, assistant professor at the Medical College of Wisconsin Endocrinology Center and Clinics in Menomonee Falls, and colleagues evaluated 15 patients (14 women; mean age, 49.1 years) with postsurgical recurrent Cushing’s disease (mean time to recurrence, 3.3 years) after initial remission to determine the performance of urinary free cortisol and late-night salivary cortisol measurements for detecting recurrent Cushing’s disease.

Participants were identified as having Cushing’s disease between 2008 and 2013; there was no standard for follow-up, but after remission confirmation participants were followed at least every 6 months after surgery for 2 years and then annually thereafter. Late-night salivary cortisol was the primary biochemical test to screen for recurrence, and follow-up tests with a dexamethasone suppression test, urinary free cortisol or other tests were performed if late-night salivary results were abnormal or if suspicion of recurrence was high.

Of the cohort, 80% had normal urinary free cortisol (< 45 µg/24 hours) at recurrence. Primary transphenoidal adenoma resection was performed in all participants. Evidence of pituitary adenoma on MRI at the time of recurrence was present in seven of 12 participants with normal urinary free cortisol and two of three participants with abnormal urinary free cortisol. Normal renal function was present in all participants, and 14 underwent testing with late-night salivary cortisol, dexamethasone suppression test and urinary free cortisol.

Of participants with normal urinary free cortisol at recurrence, nine had an abnormal dexamethasone suppression test (cortisol 1.8 µg/dL), and all had at least one elevated late-night salivary cortisol measurement (> 4.3 nmol/L). Mean late-night salivary cortisol was 10.2 nmol/L, and mean urinary free cortisol was 19.9 µg/24 hours.

Therapy for recurrent Cushing’s disease was administered in 11 of the 12 participants with abnormal urinary free cortisol. Adrenocorticotropic hormone (ACTH)-staining pituitary adenoma was confirmed in three participants who underwent repeat transphenoidal adenoma resection. Pharmacotherapy was administered to seven participants with normal urinary free cortisol, and two additional participants underwent bilateral adrenalectomy.

Abnormal dexamethasone suppression test was found in two participants with elevated urinary free cortisol at the time of recurrence, and two participants had confirmed abnormal late-night salivary cortisol. All three participants with elevated urinary free cortisol at the time of recurrence underwent therapy.

“This study has shown potential clinical benefit of either surgical or medical therapy in recurrent [Cushing’s disease] patients with elevations of [late-night salivary cortisol] and normal [urinary free cortisol],” the researchers wrote. “We believe that the outcomes observed in this retrospective case series suggest that the risk/benefit ratio of early treatment needs to undergo a more rigorous prospective evaluation utilizing [late-night salivary cortisol] elevation as an early biochemical marker of recurrent [Cushing’s disease].” – by Amber Cox

Disclosure: Carroll reports being a consultant for Corcept Therapeutics. Please see the full study for a list of all other authors’ relevant financial disclosures.

From http://www.healio.com/endocrinology/adrenal/news/online/%7B9ea4e4ed-6428-49b8-9b2a-11462cb21349%7D/elevated-late-night-salivary-cortisol-may-indicate-recurrent-cushings-disease

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Cushing’s syndrome: Pituitary surgery alone is the preferred treatment to improve survival

Posted on July 8, 2016 by MaryO

Background

No agreement has been reached on the long-term survival prospects for patients with Cushing’s disease. We studied life expectancy in patients who had received curative treatment and whose hypercortisolism remained in remission for more than 10 years, and identified factors determining their survival.

Methods

We did a multicentre, multinational, retrospective cohort study using individual case records from specialist referral centres in the UK, Denmark, the Netherlands, and New Zealand. Inclusion criteria for participants, who had all been in studies reported previously in peer-reviewed publications, were diagnosis and treatment of Cushing’s disease, being cured of hypercortisolism for a minimum of 10 years at study entry, and continuing to be cured with no relapses until the database was frozen or death. We identified the number and type of treatments used to achieve cure, and used mortality as our primary endpoint. We compared mortality rates between patients with Cushing’s disease and the general population, and expressed them as standardised mortality ratios (SMRs). We analysed survival data with multivariate analysis (Cox regression) with no corrections for multiple testing.

Read more at http://www.univadis.com/viewarticle/cushing-s-syndrome-pituitary-surgery-alone-is-the-preferred-treatment-to-improve-survival-421761

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Cushing’s Syndrome Masquerading as Treatment Resistant Depression

Posted on July 4, 2016 by MaryO
Indian J Psychol Med. 2016 May-Jun; 38(3): 246–248.
PMCID: PMC4904762
B. N. Anil Kumar and Sandeep Grover1
Author information ► Copyright and License information ►

Abstract

Treatment resistant depression (TRD) is a common clinical occurrence among patients treated for major depressive disorder. A significant proportion of patients remain significantly depressed in spite of aggressive pharmacological and psychotherapeutic approaches. Management of patient with treatment resistant depression requires thorough evaluation for physical causes. We report a case of recurrent depressive disorder, who presented with severe depressive episode without psychotic symptoms, not responding to multiple adequate trials of antidepressants, who on investigation was found to have Cushing’s syndrome and responded well to Ketoconazole.

Keywords: Antiglucocorticoid drugs, Cushing’s syndrome, treatment-resistant depression

INTRODUCTION

The main aim of management of depression is remission of the episode. However, in a proportion of the patients with major depression, despite the use of adequate antidepressant doses for the adequate duration, clinical remission is not achieved. Although there is no consensus, but in general it is accepted that those patients with major depression who do not respond to 2-3 adequate trials of antidepressants are considered to have treatment-resistant depression (TRD).[1] Some of the authors[2] have suggested staging for TRD and based on the level of nonresponse the patient is allocated to different stages of TRD. The prevalence of TRD varies depending on the stage.[1] It is suggested that whenever a patient present’s with TRD, a thorough evaluation needs to be done to evaluate the underlying organic and psychosocial causes.[1] We here, report a case of recurrent depressive disorder, current episode severe depressive episode without psychotic symptoms, who did not respond to adequate trials of antidepressants and showed minimal response to electroconvulsive therapy (ECT). In view of the lack of remission, on investigation she was found to have adrenal adenoma and raised cortisol levels. She was managed with ketoconazole 400 mg/day along with the continuation of antidepressants with which she achieved remission.

CASE REPORT

Mrs. A, 40-year-old, known case of recurrent depressive disorder, with first episode occurring at the age of 36 years, with two episodes in the past which responded to antidepressant treatment, presented with severe depressive episode without psychotic symptoms of 18 months duration. For the current episode, the onset was insidious with the evolution of symptoms over the period of 1-month, without any precipitating event and the course was continuous for the current episode. Her clinical presentation was characterized by persistent sadness of mood with morning worsening, poor interaction, anhedonia, lethargy, psychomotor retardation, sleep disturbance in the form of difficulty in falling asleep with frequent midnight awakenings, reduced appetite associated with weight loss of 3 kg, reduced libido, ideas of guilt, suicidal ideations, suicidal planning with one unsuccessful attempt and off and on anxiety symptoms. Her treatment history revealed that during the current episode she was treated with tablet paroxetine 12.5-37.5 mg/day for 4 months, tablet mirtazapine 15-30 mg/day for 3 months, tablet imipramine up to 175 mg/day for 5 months, C. venlafaxine up to 300 mg/day for 2 months with no response. Later she was treated with C. venlafaxine 300 mg/day along with thyroxine 75 µg/day (for 2 months) and C. venlafaxine 300 mg/day and lithium 600 mg/day for a period of 2 months but with minimal improvement. Her compliance with the medication throughout was satisfactory.

Her general physical examination and systemic examination were normal. On mental status examination, she had sadness of mood, psychomotor retardation, ideas of hopelessness, worthlessness, guilt, and suicidal ideas. Investigations in the form of hemogram, liver function test, renal function test, serum electrolytes, thyroid function test, serum vitamin B12 levels were did not reveal any abnormality. Her magnetic resonance imaging (MRI) scan of the brain did not show any abnormality. Her psychosocial history did not reveal any evidence of chronic stressors and her family was very supportive. There was no history suggestive of mania, psychotic symptoms, alcohol or drug abuse, seizure, head injury, and cognitive decline. Her Hamilton Depression Rating scale (HDRS) score was 35.

She was continued on C. venlafaxine 300 mg/day along with tablet lithium carbonate 300 mg/day (with serum levels in the therapeutic range). In addition, due to lack of response to adequate doses of antidepressants she was treated with 14 sessions of modified ECT over the period of 6 weeks with minimal improvement (HDRS score reduced to 32). In view of the lack of response to ECT, further investigations were done for Cushing’s syndrome although her physical examination was not suggestive of the same. Workup for Cushing’s syndrome revealed raised plasma cortisol level (722.7 nmol/L [normal range 193-634 nmol/L]), dexamethasone nonsuppression and reduced plasma adreno corticotrophin hormone. MRI scan of the abdomen revealed small homogenous, well-defined lesion measuring 2 cm in the adrenal cortex with clear margins suggestive of an adrenal adenoma. She was advised surgical intervention for the same. However, she was reluctant for the same. As a result, she was started on tablet ketoconazole 200 mg/day and increased to 400 mg/day over next 15 days along with the continuation of C. venlafaxine 300 mg/day. Patient improvement was monitored clinically and using HAM-D score. Over a period of next 4 weeks, the patient showed significant improvement in her depressive symptoms with no associated side effects. Her HDRS score reduced from 32 to 5. After remission she was clinically monitored. She has been maintaining well on tablet ketoconazole 400 mg/day and of C. venlafaxine 225 mg/day for the last 4 years. Her adrenal mass has been monitored with no increase in the size of the tumor.

DISCUSSION

According to the staging of TRD by Thase and Rush,[2] the index case can be considered as stage-5 TRD, that is, patient who has not responded to antidepressants of two different classes, tricyclic antidepressants and ECT. In addition, the patient had also not responded to augmentation with thyroxine and lithium. It is suggested that whenever a patient presents with TRD, first there is a need to evaluate the patient for pseudo-resistance. The factors that contribute to pseudo-resistance include poor compliance, inadequate dosing, and discontinuation of antidepressant before adequate duration.[3] The history of the index case did not reveal the same. In view of the stage-5 nonresponse, she was empirically evaluated for Cushing’s syndrome and was found to have positive evidence for the same. Addition of ketoconazole led to remission of the episode.

Due to the role of stress and involvement of cortisol in understanding the etiopathogenesis of depression, researchers have used antiglucocorticoid drugs such as metyrapone, aminoglutethimide, ketoconazole, and Mifepristone in the management of TRD. In a review, which included 11 studies, authors reported that 67-77% of the patients show at least a partial antidepressant response and largest two series documenting response rates of 70-73%.[4]

Our case highlights the fact that while dealing with patients with TRD, psychiatrists should look into all possible medical causes for depression. Further, our case suggests that antiglucocorticoid medications can be considered in patients with TRD who do not respond to conventional treatments.

Footnotes

Source of Support: Nil

Conflict of Interest: None.

REFERENCES

1. Nemeroff CB. Prevalence and management of treatment-resistant depression. J Clin Psychiatry. 2007;68(Suppl 8):17–25. [PubMed]
2. Thase ME, Rush AJ. When at first you don’t succeed: Sequential strategies for antidepressant nonresponders. J Clin Psychiatry. 1997;58(Suppl 13):23–9. [PubMed]
3. Souery D, Papakostas GI, Trivedi MH. Treatment-resistant depression. J Clin Psychiatry. 2006;67(Suppl 6):16–22. [PubMed]
4. Wolkowitz OM, Reus VI. Treatment of depression with antiglucocorticoid drugs. Psychosom Med.1999;61:698–711. [PubMed]
Articles from Indian Journal of Psychological Medicine are provided here courtesy of Medknow Publications
From http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4904762/

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