Intraoperative MRI improves complete resection of pituitary macroadenoma

A 63-year-old man was referred to the Massachusetts General Hospital Neuroendocrine & Pituitary Tumor Clinical Center for management of a pituitary macroadenoma. He experienced increasingly severe retro-orbital headaches in the past year. He reported no double vision, fatigue, orthostatic dizziness, change in beard growth or reduction in libido. An outside head CT scan showed an enlarged pituitary gland.

Imaging and laboratory tests

A pituitary MRI with magnified pituitary slices and gadolinium contrast was ordered. A well-circumscribed “snowman-shaped” sellar mass was identified, measuring 2.6 cm x 2 cm x 1.8 cm (anteroposterior x transverse x craniocaudal) with suprasellar extension (Figure 1). The lesion was heterogeneous on T1-weighted scans after enhancement with IV gadolinium contrast. An area of hypointensity in the superior margin was consistent with a small area of cystic or hemorrhagic degeneration.

Although the mass did not extend laterally into the cavernous sinus, the sellar mass extended upward into the suprasellar cistern through a hole in the dural, the diaphragma sellae, to compress the optic chiasm. The restriction of adenoma growth by the diaphragma sellae results in the snowman shape of the macroadenoma. The optic chiasm and infundibulum (pituitary stalk) could not be identified on coronal or sagittal images (Figure 1). Visual field on confrontation suggested lateral field deficits (bilateral lateral hemianopsia) that were confirmed on formal Goldmann kinetic perimetry visual fields.

Figure 1. Preoperative MRI scan. A large “snowman-shaped” pituitary adenoma (green arrow) has heterogeneous enhancement after gadolinium contrast administration. A small hypodense area in the adenoma likely represented hemorrhage/cystic degeneration (yellow arrow). The tumor does not surround the carotid siphon, an S-shaped portion of the internal carotid artery (red arrows) within the cavernous sinus located laterally from the sella turcica where the pituitary gland resides. (A) Coronal image. (B) Sagittal image. Abbreviation: SS = spenoid sinus.

Source: Stephanie L. Lee, MD, PhD, ECNU. Reprinted with permission.

Initial hormonal evaluation was normal and included morning adrenocorticotropic hormone 18 pg/mL, cortisol 13.64 µg/dL, thyroid-stimulating hormone 2.14 uIU/mL, free thyroxine 1.2 ng/dL and prolactin 12.6 ng/mL. The patient’s morning testosterone level was normal at 324 ng/dL, with follicle-stimulating hormone 2.4 mIU/mL and luteinizing hormone 1.6 mIU/mL. His insulin-like growth factor I level was normal at 124 ng/mL.

Tumor resection

The patient was treated preoperatively with stress-dose hydrocortisone 50 mg. He then underwent transsphenoidal pituitary tumor resection. After the surgeon believed there was an adequate excision of the tumor, the extent of tumor resection was confirmed by an intraoperative MRI (Figure 2 on page 8).

Figure 2. Intraoperative MRI scan. The large macroadenoma is not seen after transsphenoidal surgery. The optic chiasm (yellow arrow) can be seen after removal of the tumor. (A) Coronal image. (B) Sagittal image. Abbreviation: SS = spenoid sinus.

The operation was concluded after the imaging confirmed the complete resection of the pituitary adenoma. The patient’s postoperative course was uneventful. Imaging 4 weeks after the resection confirmed complete resection of the suprasellar mass with residual enhancement of the resection bed and sphenoid sinuses (Figure 3 on page 8). The postoperative MRI revealed a normal optical chiasm and a downward tending of the infundibulum to the residual pituitary gland located inferiorly along the sella turcica (pituitary fossa) of the sphenoid bone. Pathology confirmed a pituitary adenoma. His anterior and posterior pituitary function were normal 6 weeks postoperatively, and his visual field deficit improved.

Intraoperative MRI

Imaging like that used in this case occurs in a specially designed operating room that allows MRI scans during surgery without moving the patient from the surgical table. The MRI is kept in a shielded enclosure during the procedure and then moved along a track into the operating room for imaging. Clinical indications for the use of intraoperative MRI in neurosurgery include resection of pituitary macroadenomas. In the past, these tumors underwent transsphenoidal resection, and the postoperative MRI was performed after 1 or more days after the procedure to check for complete removal. If residual tumor was found, the patients underwent watchful waiting, external radiation or repeat surgery.

The strategic advantage of an intraoperative MRI is that the imaging is performed during the operative procedure, and if there is any residual tumor, surgery can be resumed after the MRI is moved back into the shielded enclosure.

Figure 3. Four-week postoperative MRI scan. The large macroadenoma is not seen after the transsphenoidal survey. The optic chiasm and infundibulum (pituitary stalk) can be seen after resection of the tumor. The pituitary stalk is deviated to the left of the sella where the residual normal thyroid is locate along the sella turcica. The floor of the sella enhances with gadolinium infusion after surgery due to postoperative inflammation. (A) Coronal image. (B) Sagittal image. Abbreviation: SS = spenoid sinus.

It has been reported that the use of intraoperative MRI does not increase complication rates compared with conventional transsphenoidal surgery. Reports on the improvement of gross tumor resection using intraoperative MRI are variable, perhaps due to the expertise of the surgeon. Several reports suggest the use of intraoperative MRI allowed additional resection of noninvasive macroadenomas in 67% to 83% of the patients with a gross tumor resection. These results suggest that a substantial volume reduction and increased gross tumor resection of pituitary macroadenomas occurs with the use of intraoperative MRI compared with standard surgery. One study demonstrated that the gross tumor resection rates of invasive tumors was also improved with the use of intraoperative MRI compared with usual preoperative imaging and surgery (25% vs. 7%).

The use of intraoperative MRI, especially with transsphenoidal reoperations for invasive and noninvasive pituitary macroadenomas, leads to significantly higher “gross tumor resection” rates. This method prevents additional operations or treatment, such as radiation, because it reduces the number of patients with residual adenoma after surgery. This technology is usually found in specialized tertiary care hospitals but should be considered for reoperation for large pituitary macroadenomas or initial operation for large invasive pituitary macroadenomas.

Disclosures: Lee and Swearingen report no relevant financial disclosures.

From https://www.healio.com/endocrinology/neuroendocrinology/news/print/endocrine-today/%7B23183444-4d29-477b-844f-6eb995ac74f4%7D/intraoperative-mri-improves-complete-resection-of-pituitary-macroadenoma

Osilodrostat maintained cortisol control in Cushing’s syndrome

Osilodrostat, a drug that normalized cortisol in 89% of patients with Cushing’s syndrome who took it during a phase II study, continued to exert a sustained benefit during a 31-month extension phase.

In an intent-to-treat analysis, all of the 16 patients who entered the LINC-2 extension study responded well to the medication, with no lapse in cortisol control, Rosario Pivonello, MD, said at the annual meeting of the Endocrine Society.

“We also saw significant improvements in systolic and diastolic blood pressure and decreases in fasting plasma glucose,” said Dr. Pivonello of the University of Naples Federico II, Italy. “Surprisingly, after 31 months, we also observed declines in body mass index and weight.”

Osilodrostat, made by Novartis, is an oral inhibitor of 11 beta–hydroxylase. The enzyme catalyzes the last step of cortisol synthesis in the adrenal cortex. The drug was granted orphan status in 2014 by the European Medicines Agency.

In the LINC-2 study, 19 patients took osilodrostat at an initial dose of either 4 mg/day or 10 mg/day, if baseline urinary-free cortisol exceeded three times the upper normal limit. The dose was escalated every 2 weeks to up to 60 mg/day, until cortisol levels were at or below the upper limit of normal. In this study, the main efficacy endpoint was normalization of cortisol, or at least a 50% decrease from baseline at weeks 10 and 22.

Overall response was 89%. Osilodrostat treatment reduced urinary-free cortisol in all patients, and 79% had normal cortisol levels at week 22. The most common adverse events were asthenia, adrenal insufficiency, diarrhea, fatigue, headache, nausea, and acne. New or worsening hirsutism and/or acne were reported among four female patients, all of whom had increased testosterone levels.

The LINC-2 extension study enrolled 16 patients from the phase II cohort, all of whom had responded to the medication. They were allowed to continue on their existing effective dose through the 31-month period.

Dr. Pivonello presented response curves that tracked cortisol levels from treatment initiation in the LINC-2 study. The median baseline cortisol level was about 1,500 nmol per 24 hours. By the fourth week of treatment, this had normalized in all of the patients who entered the extension phase. The response curve showed continued, stable cortisol suppression throughout the entire 31-month period.

Four patients dropped out during the course of the study. Dr. Pivonello didn’t discuss the reasons for these dropouts. He did break down the results by response, imputing the missing data from these four patients. In this analysis, the majority (87.5%) were fully controlled, with urinary-free cortisol in the normal range. The remainder were partially controlled, experiencing at least a 50% decrease in cortisol from their baseline levels. These responses were stable, with no patient experiencing loss of control over the follow-up period.

The 12 remaining patients are still taking the medication, and they experienced other clinical improvements as well. Systolic blood pressure decreased by a mean of 2.2% (from 130 mm Hg to 127 mm Hg). Diastolic blood pressure also improved, by 6% (from 85 mm Hg to 80 mm Hg).

Fasting plasma glucose dropped from a mean of 89 mg/dL to 82 mg/dL. Weight decreased from a mean of 84 kg to 74 kg, with a corresponding decrease in body mass index, from 29.6 kg/m2 to 26.2 kg/m2.

Serum aldosterone decreased along with cortisol, dropping from a mean of 168 pmol/L to just 19 pmol/L. Adrenocorticotropic hormone increased, as did 11-deoxycortisol, 11-deoxycorticosterone, and testosterone.

Pituitary tumor size was measured in six patients. It increased in three and decreased in three. Dr. Pivonello didn’t discuss why this might have occurred.

The most common adverse events were asthenia, adrenal insufficiency, diarrhea, fatigue, headache, nausea, and acne. These moderated over time in both number and severity.

However, there were eight serious adverse events among three patients, including prolonged Q-T interval on electrocardiogram, food poisoning, gastroenteritis, headache, noncardiac chest pain, symptoms related to pituitary tumor (two patients), and uncontrolled Cushing’s syndrome.

Two patients experienced hypokalemia. Six experienced mild events related to hypocortisolism.

Novartis is pursuing the drug with two placebo-controlled phase III studies (LINC-3 and LINC-4), Dr. Pivonello said. An additional phase II study is being conducted in Japan.

Dr. Pivonello has received consulting fees and honoraria from Novartis, which sponsored the study.

Diagnosis and Treatment of Pituitary Adenomas

A Review
JAMA. 2017;317(5):516-524. doi:10.1001/jama.2016.19699

Importance  Pituitary adenomas may hypersecrete hormones or cause mass effects. Therefore, early diagnosis and treatment are important.

Observations  Prevalence of pituitary adenomas ranges from 1 in 865 adults to 1 in 2688 adults. Approximately 50% are microadenomas (<10 mm); the remainder are macroadenomas (≥10 mm).

Mass effects cause headache, hypopituitarism, and visual field defects. Treatments include transsphenoidal surgery, medical therapies, and radiotherapy. Prolactinomas account for 32% to 66% of adenomas and present with amenorrhea, loss of libido, galactorrhea, and infertility in women and loss of libido, erectile dysfunction, and infertility in men; they are generally treated with the dopamine agonists cabergoline and bromocriptine.

Growth hormone–secreting tumors account for 8% to 16% of tumors and usually present with enlargement of the lips, tongue, nose, hands, and feet and are diagnosed by elevated insulin-like growth factor 1 levels and growth hormone levels; initial treatment is surgical. Medical therapy with somatostatin analogues, cabergoline, and pegvisomant is often also needed.

Adrenocorticotropic hormone (ACTH)–secreting tumors account for 2% to 6% of adenomas and are associated with obesity, hypertension, diabetes, and other morbidity. Measurement of a late-night salivary cortisol level is the best screening test but petrosal sinus sampling for ACTH may be necessary to distinguish a pituitary from an ectopic source.

The primary treatment of Cushing disease (hypercortisolism due to ACTH-producing adenomas, which is the cause in approximately 65% of the cases of hypercortisolism) is adenoma resection and medical therapies including ketoconazole, mifepristone, and pasireotide.

Hyperthyroidism due to thyroid-stimulating hormone–secreting tumors accounts for 1% of tumors and is treated with surgery and somatostatin analogues if not surgically cured. Clinically nonfunctioning adenomas account for 15% to 54% of adenomas and present with mass effects; surgery is generally required, although incidentally found tumors can be followed if they are asymptomatic.

Conclusions and Relevance  Patients with pituitary adenomas should be identified at an early stage so that effective treatment can be implemented. For prolactinomas, initial therapy is generally dopamine agonists. For all other pituitary adenomas, initial therapy is generally transsphenoidal surgery with medical therapy being reserved for those not cured by surgery.

Read the full text here: http://jamanetwork.com/journals/jama/article-abstract/2600472

Pituitary Issues: Irregular Periods

Q: I am 28 years old and I have not yet started my periods naturally. I have to take medicine for periods — Novelon. The doctors say that there is some problem with my hormones in the pituitary gland. Please advise me how to get normal and natural periods, because after taking the medicine I get my period, but without medicines I don’t.

A by Dr Sharmaine Mitchell: The problem you have with your menstrual period being irregular is most likely due to overproduction of the hormone prolactin by the pituitary gland in the brain. The pituitary gland can sometimes enlarge and cause an overproduction of prolactin and this can result in inappropriate milk production in the breasts (white nipple discharge), irregular menstruation or absent menstrual periods, headaches and blurred vision. The blurred vision occurs as a result of compression of the optic nerve which supplies the eyes, by the enlarged brain tumour in the pituitary gland.

You should get a magnetic resonance imaging (MRI) or CT scan of the brain and pituitary gland done. You should also test your prolactin levels to determine the extent of overproduction of the hormone.

Other investigations should include a thyroid function test (TSH), follicle stimulating hormone (FSH) and leutinizing hormone (LH), and baseline testosterone level tests.

Abnormalities in the production of thyroid hormones can also cause menstrual irregularities and this should be ruled out.

Polycystic ovarian disease can also cause irregular menstrual periods and checking the level of FSH, LH and testosterone will help to rule out this diagnosis. This condition is usually associated with excessive weight gain, abnormal male pattern distribution on the face, chest and abdomen and an increased risk for diabetes mellitus. A pelvic ultrasound to look at the structure of the ovaries and to rule out polycystic ovaries is essential.

If the pituitary gland is enlarged, then medication can be prescribed to shrink it. Bromocriptine or Norprolac are commonly used drugs which work well in reducing the prolactin levels and establishing regular menstrual cycles. The use of these drugs will also help to establish ovulation and improve your fertility.

In some cases it may become necessary to have surgery done if the tumour in the pituitary gland is large and does not respond to the usual medications prescribed to shrink the pituitary gland. The MRI of the brain and pituitary gland will give an idea as to the size of the gland and help to determine if there is a need for you to see the neurosurgeon.

In most cases medical management with drugs will work well and there is no need for surgical intervention. This is a problem that can recur, so it may be necessary to take treatment intermittently for a long period of time, especially if fertility is desired.

Consult your doctor who will advise you further. Best wishes.

Dr Sharmaine Mitchell is an obstetrician and gynaecologist. Send questions via e-mail to allwoman@jamaicaobserver.com; write to All Woman, 40-42 1/2 Beechwood Ave, Kingston 5; or fax to 968-2025. All responses are published. Dr Mitchell cannot provide personal responses.

DISCLAIMER:

The contents of this article are for informational purposes only and must not be relied upon as an alternative to medical advice or treatment from your own doctor.

From http://www.jamaicaobserver.com/magazines/allwoman/Still-no-normal-period-at-28_87596

UAE Patient’s (Pituitary) Brain Tumour Removed Through Nostrils

Dubai: A 34-year-old patient working as a crane operator has undergone a remarkable new procedure of surgery at Thumbay Hospital, Dubai, that facilitated the removal of a brain tumour through the nostrils.

The patient, Mehnaj Khan, a Pakistani crane operator, underwent endoscopic trans-nasal trans-sphenoidal surgery in September, where the tumour was removed through the nose by endoscopic surgery without any cut or stitches on the skin. The father of five children has now made a full recovery, with improved vision, a hospital spokesperson said.

Khan first noticed something was wrong when his eyesight began to diminish, first the right eye, followed by the left eye. Although he had ignored his frequent bouts of headache for two years, Khan was compelled to visit an ophthalmologist due to vision deterioration. When an eye check-up revealed nothing was wrong, he was referred to to Thumbay Hospital, where an MRI scan of the brain revealed that he had a large tumour in the pituitary gland, pressing on the optic apparatus of brain and also hypothalamus, a very vital part of brain. This tumour was pressing on his optic nerves, causing him to slowly lose his sight.

Dr. Ishwar Chandra Premsagar, consultant neurosurgeon at Thumbay Hospital who operated on Khan, said: “Conventionally, such operations require surgeons to open the skull — a procedure known as a craniotomy. Alternatively, affected portions of the brain are reached via major incisions in the side of the face or inside the mouth, leaving behind major scars of the surgery. However, the patient’s tumour was removed by suctioning it out through his nose.”

An ear nose and throat (ENT) surgeon and an eye surgeon were consulted to plan the surgery and save further deterioration of vision while providing a chance for complete recovery.

Khan, who was nearly blind in one eye with the tumour growth, expressed his gratitude to the hospital and the teams of surgeons as he noticed improvement in his vision after the surgery. By the end of the week, he could read too. The patient was very thankful to the team of surgeons.

Dr Premsagar added: “The endoscope provides a close-up view of the pituitary, allowing the surgeon to remove the entire tumour out in one go through the nostrils, causing no disfigurement or damage to the brain. On the other hand, the procedure ensures far less danger of brain damage or stroke, and the patient usually makes a quicker recovery. Although post-surgery, deterioration of vision stops, but one cannot guarantee complete recovery of vision. This patient was lucky as his vision improved, but it may not happen in all patients. Hence, it is extremely important that one should ensure early consultation, diagnosis and surgery to ensure high chances of recovery.”

From http://gulfnews.com/news/uae/health/uae-patient-s-brain-tumour-removed-through-nostrils-1.1933841

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