Category Archives: Cranial Base

Update: Prolactinoma Radiosurgery

Stereotactic radiosurgery also serves as an option for those refractory to medical and surgical therapy 1).

GKRS plays a significant role in the treatment of non-functioning [NFA] and hormonal-active [HAA] pituitary adenoma. It affords high rate of tumor control and offers low risk of collateral neurological or endocrine axis injury. A study showed that control of tumor growth was achieved in 90% patients, shrinkage of tumor in 54% and arrest of progression in 36% cases after GKRS treatment. The biochemical remission rate in GH secreting adenoma was 57%, ACTH adenoma was 67% and prolactinoma was 40%. Age less than 50 years and tumor volume less than 5cm3 were associated with a favourable radiosurgical outcome 2).

Case series

2015

Radiotherapy as an alternative and adjuvant treatment for prolactinomas has been performed at the Department of Radiation Oncology, Prince of Wales Cancer Centre, Sydney, New South Wales, Australia, with the linear accelerator since 1990.

In a retrospective review of 13 patients managed with stereotactic radiosurgery (SRS) and 5 managed with fractionated stereotactic radiotherapy (FSRT), as well as 5 managed with conventional radiotherapy, at the Prince of Wales Hospital. Patients with a histopathologically diagnosed prolactinoma were eligible. Those patients who had a confirmed pathological diagnosis of prolactinoma following surgical intervention, a prolactin level elevated above 500 μg/L, or a prolactin level persistently elevated above 200 μg/L with exclusion of other causes were represented in this review.

At the end of documented follow-up (SRS median 6 years, FSRT median 2 years), no SRS patients showed an increase in tumour volume. After FSRT, 1 patient showed an increase in size, 2 showed a decrease in size and 2 patients showed no change. Prolactin levels trended towards improvement after SRS and FSRT, but no patients achieved the remission level of <20 μg/L. Seven of 13 patients in the SRS group achieved a level of <500 μg/L, whereas no patients reached this target after FSRT.

A reduction in prolactin level is frequent after SRS and FSRT for prolactinomas; however, true biochemical remission is uncommon. Tumour volume control in this series was excellent, but this may be related to the natural history of the disease. Morbidity and mortality after stereotactic radiation were very low in this series 3).


Cohen-Inbar et al., reviewed the outcome of patients with medically and surgically refractory prolactinomas treated with Gamma Knife radiosurgery (GKRS) during a 22 years follow-up period.

They reviewed the patient database at the University of Virginia Gamma Knife center during a 25-year period (1989-2014), identifying 38 patients having neurosurgical, radiological and endocrine follow-up.

Median age at GKRS treatment was 43 years. Median follow-up was 42.3 months (range 6-207.9). 55.3 % (n = 21) were taking a dopamine agonist at time of GKRS. 63.2 % (n = 24) had cavernous sinus tumor invasion. Endocrine remission (normal serum prolactin off of a dopamine agonist) was achieved in 50 % (n = 19). GKRS induced hypopituitarism occurred in 30.3 % (n = 10). Cavernous sinus involvement was shown to be a significant negative prognosticator of endocrine remission. Taking a dopamine agonist drug at the time of GKRS showed a tendency to decrease the probability for endocrine remission.

GKRS for refractory prolactinomas can lead to endocrine remission in many patients. Hypopituitarism is the most common side effect of GKRS 4).

2013

evaluated the efficacy of Gamma knife stereotactic radiosurgery (GKSR) as an adjunctive management modality for patients with drug resistant or intolerant cavernous sinus invasive prolactinomas. Twenty-two patients with cavernous sinus invasive prolactinoma underwent GKSR between 1994 and 2009. Thirteen patients were dopamine agonist (DA) resistant. Six patients were intolerant to DA. Three patients chose GKSR as their initial treatment modality in hopes they might avoid life long suppression medication. The median tumor volume was 3.0 cm3 (range 0.3–11.6). The marginal tumor dose (median= 15 Gy, range 12–25 Gy) prescribed was based on the dose delivered to the optic apparatus. The median follow-up interval was 36 months (range, 12–185). Endocrine normalization was defined as a normal serum prolactin level off DA (cure) or on DA. Endocrine improvement was defined asa decreased but still elevated serum prolactin level. Endocrine deterioration was defined as an increased serum prolactin level. Endocrine normalization was achieved in six(27.3%) patients. Twelve (54.5%) patients had endocrine improvement. Four patients (18.2%) developed delayed increased prolactin. Imaging-defined local tumor control was achieved in 19 (86.4%) patients, 12 of whom had tumor regression. Three patients had a delayed tumor progression and required additional management. One patient developed a new pituitary axis deficiency after GKSR. Invasive prolactinomas continue to pose management challenges. GKSR is a non invasive adjunctive option that may reduce prolactin levels in patients who are resistant to or intolerant of suppression medication. In a minority of cases, patients may no longer require long term suppression therapy 5).

2006

Twenty-three patients were included in analysis of endocrine outcomes (median and average follow-up of 55 and 58 mo, respectively) and 28 patients were included in analysis of imaging outcomes (median and average follow-up of 48 and 52 mo, respectively). Twenty-six percent of patients achieved a normal serum prolactin (remission) with an average time of 24.5 months. Remission was significantly associated with being off of a dopamine agonist at the time of GKRS and a tumor volume less than 3.0 cm3 (P < 0.05 for both). Long-term image-based volumetric control was achieved in 89% of patients. Complications included new pituitary hormone deficiencies in 28% of patients and cranial nerve palsy in two patients (7%).

Clinical remission in 26% of treated patients is a modest result. However, because the GKRS treated tumors were refractory to other therapies and because complication rates were low, GKRS should be part of the armamentarium for treating refractory prolactinomas. Patients with tumors smaller than 3.0 cm3 and who are not receiving dopamine agonist at the time of treatment will likely benefit most 6).

2000

Twenty patients with prolactinomas were followed after GKS. Five patients were treated successfully; their prolactin (PRL) levels dropped into the normal range and dopaminergic drugs could be discontinued. Two spontaneous pregnancies were observed and 11 patients experienced improvement. Improvement was defined as normal PRL levels with the continued possibility of reduced medical treatment or a substantially reduced medical treatment dose with some degree of hyperprolactinemia maintained. The treatment failed in three patients who experienced no improvement. Patients treated with dopaminergic drugs during GKS did significantly less well in comparison with the untreated group when a cumulative distribution function (Kaplan-Meier estimate) was used. CONCLUSIONS:

The results of GKS for prolactinomas in this investigation are better than the results published by others. This may be an effect of case selection because there were no “salvage cases” in our group of patients. Because a dopamine agonist seemed to induce radioprotection in this series, it is suggested that GKS be performed during an intermission in drug therapy when the dopamine agonist is discontinued 7).

1)

Wong A, Eloy JA, Couldwell WT, Liu JK. Update on prolactinomas. Part 2: Treatment and management strategies. J Clin Neurosci. 2015 Oct;22(10):1568-74. doi: 10.1016/j.jocn.2015.03.059. Epub 2015 Aug 1. Review. PubMed PMID: 26243714.

2)

Narayan V, Mohammed N, Bir SC, Savardekar AR, Patra DP, Bollam P, Nanda A. Long term Outcome of Non-functioning and Hormonal-active Pituitary Adenoma after Gamma Knife Radio Surgery. World Neurosurg. 2018 Mar 21. pii: S1878-8750(18)30576-X. doi: 10.1016/j.wneu.2018.03.094. [Epub ahead of print] PubMed PMID: 29574220.

3)

Wilson PJ, Williams JR, Smee RI. Single-centre experience of stereotactic radiosurgery and fractionated stereotactic radiotherapy for prolactinomas with the linear accelerator. J Med Imaging Radiat Oncol. 2015 Jun;59(3):371-8. doi: 10.1111/1754-9485.12257. Epub 2014 Nov 20. PubMed PMID: 25410143.

4)

Cohen-Inbar O, Xu Z, Schlesinger D, Vance ML, Sheehan JP. Gamma Knife radiosurgery for medically and surgically refractory prolactinomas: long-term results. Pituitary. 2015 Dec;18(6):820-30. doi: 10.1007/s11102-015-0658-1. PubMed PMID: 25962347.

5)

Liu X, Kano H, Kondziolka D, Park KJ, Iyer A, Shin S, Niranjan A, Flickinger JC, Lunsford LD. Gamma knife stereotactic radiosurgery for drug resistant or intolerant invasive prolactinomas. Pituitary. 2013 Mar;16(1):68-75. PubMed PMID: 22302560.

6)

Pouratian N, Sheehan J, Jagannathan J, Laws ER Jr, Steiner L, Vance ML. Gamma knife radiosurgery for medically and surgically refractory prolactinomas. Neurosurgery. 2006 Aug;59(2):255-66; discussion 255-66. PubMed PMID: 16883166.

7)

Landolt AM, Lomax N. Gamma knife radiosurgery for prolactinomas. J Neurosurg. 2000 Dec;93 Suppl 3:14-8. PubMed PMID: 11143231.

Update: Desmopressin

Desmopressin

Desmopressin, sold under the trade name DDAVP among others, is a medication used to treat diabetes insipidus, bedwetting, hemophilia A, von Willebrand disease, and high blood urea levels.

In hemophilia A and von Willebrand disease, it should only be used for mild to moderate cases.

It may be given in the nose, by injection into a vein, by mouth, or under the tongue.

More potent and longer acting than vasopressin.

In patients with central diabetes insipidus DI, desmopressin is the drug of choice.

A synthetic analogue of antidiuretic hormone (ADH), desmopressin is available in subcutaneous, IV, intranasal, and oral preparations.

Generally, it can be administered 2-3 times per day. Patients may require hospitalization to establish fluid needs. Frequent electrolyte monitoring is recommended during the initial phase of treatment.

Alternatives to desmopressin as pharmacologic therapy for DI include synthetic vasopressin and the nonhormonal agents chlorpropamide, carbamazepine, clofibrate (no longer on the US market), thiazides, and nonsteroidal anti-inflammatory drugs (NSAIDs). Because of side effects, carbamazepine is rarely used, being employed only when all other measures prove unsatisfactory. NSAIDs (eg, indomethacin) may be used in nephrogenic DI, but only when no better options exist. In central DI, the primary problem is a hormone deficiency; therefore, physiologic replacement with desmopressin is usually effective. Use a nonhormonal drug for central DI if response is incomplete or desmopressin is too expensive.

Indications

Desmopressin (DDAVP) is a well-known hemostatic agent, and recent guidelines already suggest its use in individuals exposed to antiplateletdrugs.

Francoeur et al. hypothesized that DDAVP administration in patients with SAH at admission would be associated with lower risks of intracranial aneurysm rebleeding.

They performed an observational cohort study of patients enrolled in the Columbia University SAH Outcome Project between August 1996 and July 2015. They compared the rate of rebleeding between patients who were and those who were not treated with DDAVP. After adjustment for known predictors, logistic regression was used to measure the association between treatment with DDAVP and risks of rebleeding.

Among 1639 patients with SAH, 12% were treated with DDAVP. The main indication for treatment was suspected exposure to an antiplatelet agent. The overall incidence of rebleeding was 9% (1% among patients treated with DDAVP compared with 8% among those not treated). After adjustment for antiplatelet use and known predictors, treatment with DDAVP was associated with a 45% reduction in the risks of rebleeding (adjusted OR 0.55, 95% CI 0.27-0.97). DDAVP was associated with a higher incidence of hyponatremia but not with thrombotic events or delayed cerebral ischemia.

Treatment with DDAVP was associated with a lower risk of rebleeding among patients with SAH. These findings support further study of DDAVP as first-line therapy for medical hemostasis in patients with SAH 1).


Desmopressin seems to be an effective and accepted as well as frequently adopted measure to antagonize the aspirin effect on platelet function during various major surgical procedures 2).


Bilateral inferior petrosal sinus sampling (IPSS) with desmopressin is a sensitive approach in the diagnosis of Cushing’s disease (CD) and has moderate accuracy in tumour lateralization, making it an alternative choice to IPSS with CRH 3).

1)

Francoeur CL, Roh D, Schmidt JM, Mayer SA, Falo MC, Agarwal S, Connolly ES, Claassen J, Elkind MSV, Park S. Desmopressin administration and rebleeding in subarachnoid hemorrhage: analysis of an observational prospective database. J Neurosurg. 2018 Feb 2:1-7. doi: 10.3171/2017.7.JNS17990. [Epub ahead of print] PubMed PMID: 29393750.

2)

Korinth MC, Gilsbach JM, Weinzierl MR. Low-dose aspirin before spinal surgery: results of a survey among neurosurgeons in Germany. Eur Spine J. 2007 Mar;16(3):365-72. Epub 2006 Sep 5. PubMed PMID: 16953446; PubMed Central PMCID: PMC2200713.

3)

Feng M, Liu Z, Liu X, Zhang X, Bao X, Yao Y, Deng K, Xing B, Lian W, Zhu H, Lu L, Wang R. Tumour lateralization in Cushing’s disease by inferior petrosal sinus sampling with desmopressin. Clin Endocrinol (Oxf). 2018 Feb;88(2):251-257. doi: 10.1111/cen.13505. Epub 2017 Nov 27. PubMed PMID: 29080355.

Endoscopic and Keyhole Cranial Base Surgery

Endoscopic and Keyhole Cranial Base Surgery

by James J. Evans and Tyler J. Kenning

 List Price:  $236.69
The first two sections of this text address endoscopic and keyhole surgical procedures for cranial base and deep brain structures.  These sections provide a comprehensive, state-of-the art review of this minimally invasive field and will serve as a valuable resource for clinicians, surgeons and researchers with an interest in cranial base surgery.  The philosophy, techniques, indications and limitations of endoscopic and keyhole cranial base surgery are covered in detail. This reference includes a discussion of the basic principles of these approaches as well as the preoperative planning, intraoperative pearls, and reconstruction techniques.  The thorough descriptions of the practical and technical aspects are accompanied by extensive illustrations, figures and operative images.
Extending beyond the technical details of these procedures, this text provides a third section that focuses on a thorough analysis and comparison of the endoscopic, keyhole and traditional open approaches to specific intracranial regions.  Utilizing a “target-based” approach, the utility of each surgical technique is evaluated in regard to accessing pathology of the anterior, middle and posterior fossa cranial base as well as the deep central regions of the brain. All chapters are written by experts in their fields and include the most up to date scientific and clinical information.
 Endoscopic and Keyhole Cranial Base Surgery will be a valuable resource to specialists in optimizing surgical results and improving patient outcomes.

 

Update: Superior semicircular canal dehiscence

Superior semicircular canal dehiscence

Superior semicircular canal dehiscence (SSCD) is a disorder of the skull base that is gaining increasing recognition among neurosurgeons.

Superior semicircular canal dehiscence (SSCD) is an osseous defect of the arcuate eminence of the petrous temporal bone.

With this dehiscence, the fluid in the membranous superior canal (which is located within the tubular cavity of the bony canal) can be displaced by sound and pressure stimuli, creating certain vestibular and/or auditory signs and symptoms.

Since this was first reported in 1998 by Minor and colleagues, there has been much advancement made in terms of diagnosis and treatment 1).

Diagnosis

The condition is confirmed on high-resolution computed tomography (CT) imaging.

High-resolution computed tomographic temporal bone images were imported into a freely available segmentation software. Dehiscence lengths and volumes were ascertained by independent authors. Inter-rater observer reliability was assessed using Cronbach’s alpha. Correlation and regression analyses were performed to evaluate for relationships between dehiscence size and symptoms (pre- and post-operative).

Thirty-seven dehiscences were segmented using the novel volumetric assessment. Cronbach’s alpha for dehiscence lengths and volumes were 0.97 and 0.95, respectively. Dehiscence lengths were more variable as compared to dehiscence volumes (σ 2 8.92 vs σ 2 0.55, F = 1.74). The mean dehiscence volume was 2.22 mm 3 (0.74, 0.64-0.53 mm 3 ). Dehiscence volume and headache at presentation were positively correlated ( R pb = 0.67, P = .03). Dehiscence volume and vertigo improvement after surgery were positively correlated, although this did not reach statistical significance ( R pb = 0.46, P = .21).

SSCD volumetry is a novel method of measuring dehiscence size that has excellent inter-rater reliability and is less variable compared to dehiscence length, but its potential as a predictor of symptom outcomes is not substantiated. However, the study is limited by low power 2).

MRI FIESTA scans have recently been used to image SSCD. Additionally, audiometry and vestibular evoked myogenic potential (VEMP) testing are useful screening tools.

Treatment

Currently, the middle fossa approach is the most common and standard surgical approach to repair SSCD. The transmastoid, endoscopic and transcanal or endaural approaches have also been recently utilized. Presently, there is no consensus as to the best approach, material or technique for repair of SSCD. As we learn more, newer and less invasive approaches and techniques are being used to treat SSCD 3).

Symptoms are often improved by surgical repair. Although a classic middle fossa craniotomy has been used with good results, recent advances in technique have allowed for modification of the traditional approach into a smaller skin incision and a minimally invasive middle fossa keyhole craniectomy roughly 1.7 cm in diameter.

To delineate this novel approach and describe the technique for accurate localization of the dehiscence using preoperative measurements and intraoperative image guidance, thereby minimizing the need for a larger skin incision and craniotomy.

Patients were independently diagnosed with SSCD by the senior authors. Once relevant imaging was acquired, the novel keyhole technique was performed. Patients’ vestibular and auditory symptoms before and after the procedure were assessed. Outcomes from a series of patients treated with this keyhole approach were tabulated and reported.

Twelve cases from 11 patients were included in this series. Auditory symptoms had high rates of resolution with pulsatile tinnitus, internal amplification of sounds, and autophony being resolved in a majority of cases. Only 2 cases reported hearing decline. Sound/pressure induced vertigo and disequilibrium also demonstrated high rates of resolution. No complications were reported.

The minimally invasive middle fossa keyhole craniectomy is a novel approach for the repair of SSCD. This approach may contribute to resolved auditory and vestibular symptoms with low morbidity and quick recovery 4).

Reviews

A analysis included 24 studies that described 230 patients that underwent either an middle cranial fossa (MCF) (n = 148, 64%) approach or a transmastoid approach (TM) (n = 82, 36%) for primary surgical repair of SSCD. A greater percentage of patients in the MCF group experienced resolution of auditory symptoms (72% vs 59%, p = 0.012), aural fullness (83% vs 55%, p = 0.049), hearing loss (57% vs 31%, p = 0.026), and disequilibrium (75% vs 44%, p = 0.001) when compared to the TM group. The MCF approach was also associated with higher odds of symptom resolution for auditory symptoms (odds ratio [OR] 1.79, 95% confidence interval [CI] 1.14-2.82), aural fullness (OR 4.02, 95% CI 1.04-15.53), hearing loss (OR 2.91, 95% CI 1.14-7.42), and disequilibrium (OR 3.94, 95% CI 1.78-8.73). The mean follow-up was 9 months.

The literature suggests that the MCF approach for the repair of SSCD is associated with greater symptom resolution when compared to the TM approach. This information could help facilitate patient discussions 5).

Case series

A total of 72 cases of SSCD in 60 patients were repaired via a middle fossa approach at a single institution. Main Outcome Measures  The distance from the proposed reference point to the dehiscence was statistically analyzed using Shapiro-Wilk’s goodness-of-fit test and Student’s t -test. Results  Average distance for all patients was 28.84 ± 2.22 mm (range: 22.96-33.43). Average distance for females was 29.08 mm (range: 24.56-33.43) versus 28.26 mm (range: 22.96-32.36) for males. There was no difference in distance by sex ( p  = 0.174). The distance measurements followed a normal distribution with 95% of the patients between 24.49 and 33.10 mm.

This study analyzed a potential reference point during a middle fossa approach for SSCD surgery. The distance from this reference point to the SSCD was found to be consistent and may serve as a readily identifiable landmark in localizing the dehiscence 6).

Case reports

A 35-year-old man with superior semicircular canal dehiscence treated by a joint neurosurgical and otolaryngological team 7).

1) , 3)

Mau C, Kamal N, Badeti S, Reddy R, Ying YM, Jyung RW, Liu JK. Superior semicircular canal dehiscence: Diagnosis and management. J Clin Neurosci. 2018 Feb;48:58-65. doi: 10.1016/j.jocn.2017.11.019. Epub 2017 Dec 7. Review. PubMed PMID: 29224712.
2)

Lagman C, Beckett JS, Chung LK, Chen CHJ, Voth BL, Gaonkar B, Gopen Q, Yang I. Novel Method of Measuring Canal Dehiscence and Evaluation of its Potential as a Predictor of Symptom Outcomes After Middle Fossa Craniotomy. Neurosurgery. 2017 Aug 9. doi: 10.1093/neuros/nyx430. [Epub ahead of print] PubMed PMID: 28945893.
4)

Vanessa T, Pelargos PE, Spasic M, Chung LK, Voth B, Ung N, Gopen Q, Yang I. Minimally Invasive Middle Fossa Keyhole Craniectomy for Repair of Superior Semicircular Canal Dehiscence. Oper Neurosurg (Hagerstown). 2017 Jun 1;13(3):317-323. doi: 10.1093/ons/opw046. PubMed PMID: 28521355.
5)

Nguyen T, Lagman C, Sheppard JP, Romiyo P, Duong C, Prashant GN, Gopen Q, Yang I. Middle cranial fossa approach for the repair of superior semicircular canal dehiscence is associated with greater symptom resolution compared to transmastoid approach. Acta Neurochir (Wien). 2017 Oct 11. doi: 10.1007/s00701-017-3346-2. [Epub ahead of print] Review. PubMed PMID: 29022108.
6)

Beckett JS, Chung LK, Lagman C, Voth BL, Jacky Chen CH, Gaonkar B, Gopen Q, Yang I. A Method of Locating the Dehiscence during Middle Fossa Approach for Superior Semicircular Canal Dehiscence Surgery. J Neurol Surg B Skull Base. 2017 Aug;78(4):353-358. doi: 10.1055/s-0037-1601886. Epub 2017 Apr 18. PubMed PMID: 28725523; PubMed Central PMCID: PMC5515662.
7)

Martin JE, Neal CJ, Monacci WT, Eisenman DJ. Superior semicircular canal dehiscence: a new indication for middle fossa craniotomy. Case report. J Neurosurg. 2004 Jan;100(1):125-7. PubMed PMID: 14743924.

Update: Giant GH secreting pituitary adenoma

Giant GH secreting pituitary adenoma

Patients with acromegaly usually harbor pituitary macroadenomas measuring between 10 and 30 mm in maximal diameter. Giant (adenoma size ≥40 mm) GH secreting pituitary adenoma are rarely encountered.

They are invasive, uncontrolled by surgery, and respond poorly to medical treatment. Aggressive multimodal therapy is critical for their management, enhancing control rate and biochemical remission 1).

Case series

2017

Giordano et al., present the clinical, radiological and hormonal status of three patients affected by invasive GH-secreting pituitary adenomas without clinical signs and symptoms of acromegaly with elevation of serum IGF-1 from a series of 142 pituitary adenomas operated in the Department of Neurosurgery, International Neuroscience Institute-Hannover, Germany with the aid of intraoperative magnetic resonance imaging(MRI). Total tumor removal was possible in two of the three cases; the patients show normal hormonal status and no recurrence at long-term follow-up. In the third case, due to the different features of the tumor, complete resection was not possible and a multimodal treatment was performed that allowed regularization of the hormonal status and control of the residual tumor. GH-secreting adenomas without clinical manifestation of acromegaly are uncommon lesions. Total microsurgical excision can be curative. However, in case of partial removal, a tailored adjuvant treatment should be considered to preserve the quality of life of the patient and avoid regrowth of the lesion. In not resectable tumors, preoperative medical treatment with somatostatin analogues is always an option 2).

2015

Shimon et al. identified 34 patients (15 men and 19 females) with giant adenomas among 762 subjects (4.5%) with acromegaly, and characterized their clinical characteristics and response to treatment.

Mean age at diagnosis was 34.9±12.5 years (range, 16-67 years). Mean adenoma size was 49.4±9.4 mm (range, 40-80 mm); 30 adenomas showed cavernous sinus invasion and 32 had suprasellar extension. Twenty-nine (85%) patients had visual field defects. Mean baseline IGF1 was 3.4±1.8×ULN. All patients except one underwent pituitary surgery (one to three procedures), but none achieved hormonal remission following first surgery. Among the 28 subjects with visual disturbances, 14 recovered post-operatively and 13 improved. Treatment with somatostatin analogs was given to all patients after surgical failure. Six achieved remission, nine others were partially controlled (IGF1<1.5×ULN; 3/9 when combined with cabergoline), and 17 did not respond (two were lost). Nine patients were treated with pegvisomant, alone (n=4) or in combination with somatostatin analogs (n=5); five are in remission and two are partially controlled. Pasireotide-LAR achieved hormonal remission in one of the six patients. Currently, after a mean follow-up period of 8.9 years, 17 patients are in biochemical remission, eight are partially controlled, and seven are uncontrolled (two were lost to follow-up).

Giant GH-secreting adenomas are invasive, uncontrolled by surgery, and respond poorly to medical treatment. Aggressive multimodal therapy is critical for their management, enhancing control rate and biochemical remission 3).

Case reports

A 23-year-old male patient presented with continuous increase in height during the past 6 years due to a GH-secreting giant pituitary adenoma. Because of major intracranial extension and failure of octreotide treatment to shrink the tumour, the tumour was partially resected by a trans-frontal surgical approach. At immunohistochemistry, the tumour showed a marked expression of GH and a sparsely focal expression of prolactin. Somatostatin receptors (sst) 1-5 were not detected. Tumour tissue weakly expressed dopamine receptor type 2. The Gs alpha subunit was intact. Conversion from somatostatin analogue to pegvisomant normalized insulin-like-growth-factor-I (IGF-I) levels and markedly improved glucose tolerance.

Pegvisomant is a potent treatment option in patients with pituitary gigantism. In patients who do not respond to somatostatin analogues, knowledge of the SST receptor status may shorten the time to initiation of pegvisomant treatment 4).

1)

Shimon I, Jallad RS, Fleseriu M, Yedinak CG, Greenman Y, Bronstein MD. Giant GH-secreting pituitary adenomas: management of rare and aggressive pituitary tumors. Eur J Endocrinol. 2015 Jun;172(6):707-13. doi: 10.1530/EJE-14-1117. Epub 2015 Mar 19. PubMed PMID: 25792375.
2)

Giordano M, Samii A, Fahlbusch R. Aggressive somatotrophinomas lacking clinical symptoms: neurosurgical management. Neurosurg Rev. 2017 Dec 30. doi: 10.1007/s10143-017-0940-y. [Epub ahead of print] PubMed PMID: 29290044.
3)

Shimon I, Jallad RS, Fleseriu M, Yedinak CG, Greenman Y, Bronstein MD. Giant GH-secreting pituitary adenomas: management of rare and aggressive pituitary tumors. Eur J Endocrinol. 2015 Jun;172(6):707-13. doi: 10.1530/EJE-14-1117. Epub 2015 Mar 19. PubMed PMID: 25792375.
4)

Müssig K, Gallwitz B, Honegger J, Strasburger CJ, Bidlingmaier M, Machicao F, Bornemann A, Ranke MB, Häring HU, Petersenn S. Pegvisomant treatment in gigantism caused by a growth hormone-secreting giant pituitary adenoma. Exp Clin Endocrinol Diabetes. 2007 Mar;115(3):198-202. PubMed PMID: 17427111.