Pituitary apoplexy treatment

Pituitary apoplexy treatment

Optimal pituitary apoplexy management remains controversial.

The pituitary function is consistently compromised, necessitating rapid administration of corticosteroids and endocrine evaluation.


Patients with pituitary apoplexy may have a spontaneous remission of hormonal hypersecretion. If it is not an emergency, we should delay a decision to undertake surgery following apoplexy and re-evaluate hormone secretion. Hyponatremia is an acute sign of hypocortisolism in pituitary apoplexy. However, SIADH although uncommon, could appear later as a consequence of direct hypothalamic insult and requires active and individualized treatment. For this reason, closely monitoring sodium at the beginning of the episode and throughout the first week is advisable to guard against SIADH. Despite being less frequent, if pituitary apoplexy is limited to the tumor, the patient can recover pituitary function previously damaged by the undiagnosed macroadenoma 1).


In the absence of visual deficits, prolactinomas may be treated with bromocriptine.

Rapid decompression is required for: sudden constriction of visual fields, severe and/or rapid deterioration of acuity, or neurologic deterioration due to hydrocephalus. Surgery in ≤7 days of pituitary apoplexy resulted in better improvement in ophthalmoplegia (100%), visual acuity (88%) and field cuts (95%) than surgery after 7 days, based on a retrospective study of 37 patients. 2).

Decompression is usually via a transsphenoidal route (transcranial approach may be advantageous in some cases).

A systematic literature search was performed of MedLineEmbase, the Cochrane Library, and the Web of Science for articles published between January 1992 and September 2014. Studies of the outcomes in consecutive patients that compared surgical intervention with non-surgical treatment for pituitary apoplexy were included.

Six studies met the inclusion criteria. As compared to the non-surgically treated patients, surgically treated patients had a significantly higher rate of recovery of ocular palsy and visual field (both P<0.05). However, there was no significant difference in the recovery of visual acuity and pituitary function (P>0.05) between the two groups.

The findings of this study suggest that surgical intervention should be advocated for pituitary apoplexy patients with visual field defects and ocular palsy 3).

Goals of surgery

1. To decompress the following structures if under pressure: optic apparatus, pituitary glandcavernous sinusthird ventricle (relieving hydrocephalus)

2. Obtain tissue for pathology

3. Complete removal of the tumor is usually not necessary

4. For hydrocephalus: ventricular drainage is generally required.

References

1)

Sanz-Sapera E, Sarria-Estrada S, Arikan F, Biagetti B. Acromegaly remission, SIADH and pituitary function recovery after macroadenoma apoplexy. Endocrinol Diabetes Metab Case Rep. 2019 Jul 15;2019(1). doi: 10.1530/EDM-19-0057. PubMed PMID: 31310082.
2)

Bills DC, Meyer FB, Laws ER,Jr, Davis DH, Ebersold MJ, Scheithauer BW, Ilstrup DM, Abboud CF. A retrospective analysis of pituitary apoplexy. Neurosurgery. 1993; 33:602–8; discussion 608-9
3)

Tu M, Lu Q, Zhu P, Zheng W. Surgical versus non-surgical treatment for pituitary apoplexy: A systematic review and meta-analysis. J Neurol Sci. 2016 Nov 15;370:258-262. doi: 10.1016/j.jns.2016.09.047. Review. PubMed PMID: 27772771.

Clinically Nonfunctioning Pituitary Adenoma Outcome

Clinically Nonfunctioning Pituitary Adenoma Outcome

Clinically nonfunctioning pituitary macroadenomas, although benign in nature, need individualized treatment and lifelong radiological and endocrinological follow-up 1).

There are anecdotal reports of tumor shrinkage during therapy with either dopamine agonists or somatostatin agonists; however tumor response to medical treatment is not reliable. For most patients, transsphenoidal resection of the tumor is the preferable primary treatment. Surgery improves visual deficits in the majority of patients and a lesser number will recover pituitary function. In the past, pituitary radiation was commonly administered following pituitary surgery; however the need for routine radiation has been reevaluated. Although tumor recurrence at 10 years post surgery may be as high as 50%, few patients with recurrence will have clinical symptoms. Close follow-up with surveillance pituitary scans should be performed after surgery and radiation therapy reserved for patients having significant tumor recurrence 2).


Hypopituitarism is observed in NFPAs due to tumour- or treatment-related factors and may increase mortality risk.

The main aim of surgical treatment is improvement of visual function, which is achieved in over 80% of cases 3) 4).

Studies on the effect of surgery in NFMA on pituitary function show conflicting results. Some studies report, to a variable degree, an improvement in pituitary function 5) 6) 7) 8) 9) 10), whereas others could not demonstrate significant improvement in pituitary function, or even showed decreased pituitary function after transsphenoidal surgery 11) 12) 13).

The microscopic and endoscopic techniques provide similar outcomes in the surgical treatment of Knosp Grades 0-2 nonfunctioning pituitary macroadenomas 14)

The surgical removal of a nonfunctioning pituitary macroadenoma (NFP-Mac) is often incomplete.

Studies on the effect of surgery in NFMA on pituitary function show conflicting results. Some studies report, to a variable degree, an improvement in pituitary function.

Quality of Life

The QOL of NFMA patients is affected both physically and mentally by surgical treatment and symptoms. This QOL assessment is important for planning treatment strategies 15).

Cognition

Patients with NFA score significantly worse on cognition compared to reference populations. Radiotherapy does not appear to have a major influence on cognition. 16).

Sleeping

Daytime sleepiness is increased despite normal sleep patterns in patients treated for NFMA 17).

Patients treated for nonfunctioning pituitary macroadenoma (NFMA) with suprasellar extension show disturbed sleep characteristics, possibly related to hypothalamic dysfunction. In addition to hypopituitarism, both structural hypothalamic damage and sleep restriction per se are associated with the metabolic syndrome, mainly due to decreased HDL-cholesterol and increased triglycerides. Risk factors included hypopituitarism and preoperative visual field defects. Hypothalamic dysfunction may explain the metabolic abnormalities, in addition to intrinsic imperfections of hormone replacement therapy. Additional research is required to explore the relation between derangements in circadian rhythmicity and metabolic syndrome in these patients 18).

Recurrence/Residual tumor

The outcome of surgical treatment of NFPAs was improved by the use of intraoperative MRI owing to more radical resection. The remission rate seems to depend on tumor characteristics. Recurrent disease might be reduced by the use of intraoperative MRI leading to more complete surgical resection of NFPAs 19).

Tumour progression rates are high in patients with postoperative remnants. Therefore, long-term monitoring is necessary to detect tumour growth, which may be asymptomatic or manifest with visual field defects and/or pituitary dysfunction. In view of the generally slow-growing nature of these tumours, yearly magnetic resonance imaging, neuro-ophthalmologic and pituitary function evaluation are appropriate during the first 3-5 years after surgery. If there is no evidence for tumour progression during this period, testing intervals may be extended thereafter 20).

see Recurrent Nonfunctioning pituitary macroadenoma


Early and effective surgical treatment is essential for rapid recovery of visual and/or hormonal deficits, particularly in symptomatic cases 21).

Tumor size and cavernous sinus extension are the main predictors for subtotal resection STR. Notably, recovery of the gonadal axis in a large proportion of patients supports the surgical resection of NFPAM in patients suffering from gonadal deficiency, even in the absence of visual field defect (VFD) 22).


Of 18 grossly complete resection was achieved in 71% of patients. Knosp grade 0-2 tumors and tumor volumes <10 cm were significantly more likely to have received a grossly complete resection. There were 7 (12%) recurrences in patients who had received grossly complete resections, with a mean time to recurrence of 53 months. Among the 23 patients who had subtotal resections, 11 (61%) progressed radiographically and 3 (17%) had symptomatic progression. Knosp score, surgical and radiographic evidence of invasion, and preoperative visual deficits were predictive of recurrence in a univariate analysis, but Knosp grade was the only independent predictor in a multivariate analysis. Kaplan Meier analysis projected a 10-year progression-free survival rate of 80% and 21% for patients with grossly total resections and subtotal resections, respectively23).

References

1)

Dekkers OM, Pereira AM, Romijn JA. Treatment and follow-up of clinically nonfunctioning pituitary macroadenomas. J Clin Endocrinol Metab. 2008 Oct;93(10):3717-26. doi: 10.1210/jc.2008-0643. Epub 2008 Aug 5. Review. PubMed PMID: 18682516.
2)

Jaffe CA. Clinically non-functioning pituitary adenoma. Pituitary. 2006;9(4):317-21. Review. PubMed PMID: 17082898.
3)

Comtois R, Beauregard H, Somma M, Serri O, Aris-Jilwan N & Hardy J. The clinical and endocrine outcome to trans-sphenoidal microsurgery of nonsecreting pituitary adenomas. Cancer 1991 68 860–866.
4)

Soto-Ares G, Cortet-Rudelli C, Assaker R, Boulinguez A, Dubest C, Dewailly D & Pruvo JP. MRI protocol technique in the optimal therapeutic strategy of non-functioning pituitary adenomas. European Journal of Endocrinology 2002 146 179–186.
5)

Marazuela M, Astigarraga B, Vicente A, Estrada J, Cuerda C, Garcia-Uria J & Lucas T. Recovery of visual and endocrine function following transsphenoidal surgery of large nonfunctioning pituitary adenomas. Journal of Endocrinological Investigation 1994 17 703–707.
6)

Arafah BM. Reversible hypopituitarism in patients with large nonfunctioning pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 1986 62 1173–1179.
7)

Greenman Y, Tordjman K, Kisch E, Razon N, Ouaknine G & Stern N. Relative sparing of anterior pituitary function in patients with growth hormone-secreting macroadenomas: comparison with nonfunctioning macroadenomas. Journal of Clinical Endocrinology and Metabolism 1995 80 1577–1583.
8)

Nomikos P, Ladar C, Fahlbusch R & Buchfelder M. Impact of primary surgery on pituitary function in patients with nonfunctioning pituitary adenomas – a study on 721 patients. Acta Neurochirurgica (Wien) 2004 146 27–35.
9)

Webb SM, Rigla M, Wagner A, Oliver B & Bartumeus F. Recovery of hypopituitarism after neurosurgical treatment of pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 1999 84 3696–3700.
10)

Arafah BM, Kailani SH, Nekl KE, Gold RS & Selman WR. Immediate recovery of pituitary function after transsphenoidal resection of pituitary macroadenomas. Journal of Clinical Endocrinology and Metabolism 1994 79 348–354.
11)

Wichers-Rother M, Hoven S, Kristof RA, Bliesener N & Stoffel-Wagner B. Non-functioning pituitary adenomas: endocrinological and clinical outcome after transsphenoidal and transcranial surgery. Experimental and Clinical Endocrinology and Diabetes 2004 112 323–327.
12)

Dekkers OM, Pereira AM, Roelfsema F, Voormolen JH, Neelis KJ, Schroijen MA, Smit JW & Romijn JA. Observation alone after transsphenoidal surgery for nonfunctioning pituitary macroadenoma. Journal of Clinical Endocrinology and Metabolism 2006 91 1796–1801.
13)

Greenman Y, Ouaknine G, Veshchev I, Reider-Groswasser II, Segev Y & Stern N. Postoperative surveillance of clinically nonfunctioning pituitary macroadenomas: markers of tumour quiescence and regrowth. Clinical Endocrinology 2003 58 763–769.
14)

Dallapiazza R, Bond AE, Grober Y, Louis RG, Payne SC, Oldfield EH, Jane JA Jr. Retrospective analysis of a concurrent series of microscopic versus endoscopic transsphenoidal surgeries for Knosp Grades 0-2 nonfunctioning pituitary macroadenomas at a single institution. J Neurosurg. 2014 Sep;121(3):511-7. doi: 10.3171/2014.6.JNS131321. Epub 2014 Jul 4. PubMed PMID: 24995783.
15)

Tanemura E, Nagatani T, Aimi Y, Kishida Y, Takeuchi K, Wakabayashi T. Quality of life in nonfunctioning pituitary macroadenoma patients before and after surgical treatment. Acta Neurochir (Wien). 2012 Oct;154(10):1895-902. doi: 10.1007/s00701-012-1473-3. Epub 2012 Aug 25. PubMed PMID: 22922980.
16)

Brummelman P, Elderson MF, Dullaart RP, van den Bergh AC, Timmer CA, van den Berg G, Koerts J, Tucha O, Wolffenbuttel BH, van Beek AP. Cognitive functioning in patients treated for nonfunctioning pituitary macroadenoma and the effects of pituitary radiotherapy. Clin Endocrinol (Oxf). 2011 Apr;74(4):481-7. doi: 10.1111/j.1365-2265.2010.03947.x. PubMed PMID: 21133979.
17)

van der Klaauw AA, Dekkers OM, Pereira AM, van Kralingen KW, Romijn JA. Increased daytime somnolence despite normal sleep patterns in patients treated for nonfunctioning pituitary macroadenoma. J Clin Endocrinol Metab. 2007 Oct;92(10):3898-903. Epub 2007 Jul 31. PubMed PMID: 17666479.
18)

Joustra SD, Claessen KM, Dekkers OM, van Beek AP, Wolffenbuttel BH, Pereira AM, Biermasz NR. High prevalence of metabolic syndrome features in patients previously treated for nonfunctioning pituitary macroadenoma. PLoS One. 2014 Mar 7;9(3):e90602. doi: 10.1371/journal.pone.0090602. eCollection 2014. PubMed PMID: 24608862; PubMed Central PMCID: PMC3946551.
19)

Hlavica M, Bellut D, Lemm D, Schmid C, Bernays RL. Impact of ultra-low-field intraoperative magnetic resonance imaging on extent of resection and frequency of tumor recurrence in 104 surgically treated nonfunctioning pituitary adenomas. World Neurosurg. 2013 Jan;79(1):99-109. doi: 10.1016/j.wneu.2012.05.032. Epub 2012 Oct 5. PubMed PMID: 23043996.
20)

Greenman Y, Stern N. How should a nonfunctioning pituitary macroadenoma be monitored after debulking surgery? Clin Endocrinol (Oxf). 2009 Jun;70(6):829-32. doi: 10.1111/j.1365-2265.2009.03542.x. Epub 2009 Feb 16. PubMed PMID: 19222490.
21)

Yildirim AE, Sahinoglu M, Ekici I, Cagil E, Karaoglu D, Celik H, Nacar OA, Belen AD. Nonfunctioning Pituitary Adenomas Are Really Clinically Nonfunctioning? Clinical and Endocrinological Symptoms and Outcomes with Endoscopic Endonasal Treatment. World Neurosurg. 2016 Jan;85:185-92. doi: 10.1016/j.wneu.2015.08.073. Epub 2015 Sep 4. PubMed PMID: 26344636.
22)

Najmaldin A, Malek M, Madani NH, Ghorbani M, Akbari H, Khajavi A, Qadikolaei OA, Khamseh ME. Non-functioning pituitary macroadenoma: surgical outcomes, tumor regrowth, and alterations in pituitary function-3-year experience from the Iranian Pituitary Tumor Registry. Hormones (Athens). 2019 Apr 27. doi: 10.1007/s42000-019-00109-5. [Epub ahead of print] PubMed PMID: 31030405.
23)

Dallapiazza RF, Grober Y, Starke RM, Laws ER Jr, Jane JA Jr. Long-term Results of Endonasal Endoscopic Transsphenoidal Resection of Nonfunctioning Pituitary Macroadenomas. Neurosurgery. 2014 Sep 24. [Epub ahead of print] PubMed PMID: 25255271.

Pituitary stalk thickening

Pituitary stalk thickening

The diagnosis of lesions determining pituitary stalk thickness is challenging, and the identification of the underlying condition may require a long-term follow-up. Thus, clinicians should readily recognize that, when the diagnosis of central diabetes insipidus has been established, specific MRI sequences should be used in the assessment of the hypothalamic-pituitary region, and whole-brain evaluation is recommended. For clinical practice, a timely diagnosis is advisable to avoid central nervous system damage, pituitary defects and the risk of dissemination of germ cell tumours or organ involvement by LCH. Proper aetiological diagnosis can be achieved via a series of steps that start with careful observation of several neuroimaging predictors and endocrine dysfunction and then progress to more sophisticated and advanced imaging techniques 1).


325 patients with pituitary stalk thickening in the tertiary teaching Ruijin Hospital between January 2012 and February 2018 were enrolled. Basic characteristics and hormonal status were evaluated. Indicators to predict etiology in patients with histological diagnoses were analyzed.

Of the 325 patients, 62.5% were females. Deficiencies in gonadotropin was most common, followed by corticotrophingrowth hormone and thyrotropin. The increase of pituitary stalk width was associated with a risk of central diabetes insipidus (OR=3.57, P<0.001) and with a combination of central diabetes insipidus and anterior pituitary deficiency (OR=2.28, P=0.029). The cut-off pituitary stalk width of 4.75 mm had a sensitivity of 69.2% and a specificity of 71.4% for the presence of central diabetes insipidus together with anterior pituitary deficiency. Six indicators (central diabetes insipidus, patterns of pituitary stalk thickening, pituitary stalk width, neutrophilic granulocyte percentage, serum sodium level and gender were used to develop a model having an accuracy of 95.7% to differentiate neoplastic from inflammatory causes.

Pituitary stalk width could indicate the presence of anterior pituitary dysfunction especially in central diabetes insipidus patients. With the use of a diagnostic model, the neoplastic and inflammatory causes of pituitary stalk thickening could be preliminarily differentiated 2).


CSF-human chorionic gonadotropin (hCG) concentrations that exceed the established reference interval (undetectable values to 0.7 IU/L) in the presence of suprasellar lesions and pituitary stalk thickening must be considered pathological, establishing the need to exclude the presence of germinoma 3).


Diabetes insipidus (DI) associated with a thickened pituitary stalk is a diagnostic challenge in the pediatric population. Langerhans Cell Histiocytosis (LCH) is a rare cause of this entity. A 4-year-old male child presented with central DI of 1-year duration, associated with a thickened pituitary stalk. The etiology for the same remained elusive as the patient had no other manifestation to suggest LCH. A year later, the patient developed a left frontal scalp swelling. Neuroradiology demonstrated multiple punched out osteolytic lesions in both the frontal bones. The infundibulum was thickened and showed post-contrast enhancement. Histology and immunohistochemistry (IHC) of the biopsy specimen confirmed LCH. The child was administered chemotherapy according to LCH protocol, which resulted in 33% reduction in the size of the skull lesions. The DI was controlled with medical management. The present case highlights the need for serial follow-up and magnetic resonance (MR) imaging that led to a diagnosis of LCH 4).

References

1)

Di Iorgi N, Morana G, Maghnie M. Pituitary stalk thickening on MRI: when is the best time to re-scan and how long should we continue re-scanning for? Clin Endocrinol (Oxf). 2015 Oct;83(4):449-55. doi: 10.1111/cen.12769. Epub 2015 Apr 6. PubMed PMID: 25759231.
2)

Ling SY, Zhao ZY, Tao B, Zhao HY, Su TW, Jiang YR, Xie J, Sun QF, Bian LG, Sun K, He NY, Yan FH, Wang WQ, Ning G, Sun LH, Liu JM. PITUITARY STALK THICKENING IN A LARGE COHORT – TOWARDS MORE ACCURATE PREDICATORS OF PITUITARY DYSFUNCTION AND ETIOLOGY. Endocr Pract. 2019 Mar 13. doi: 10.4158/EP-2018-0550. [Epub ahead of print] PubMed PMID: 30865546.
3)

González-Sánchez V, Moreno-Pérez O, Pellicer PS, Sánchez-Ortiga R, Guerra RA, Dot MM, Alfonso AM. Validation of the human chorionic gonadotropin immunoassay in cerebrospinal fluid for the diagnostic work-up of neurohypophyseal germinomas. Ann Clin Biochem. 2011 Sep;48(Pt 5):433-7. doi: 10.1258/acb.2010.010074. PubMed PMID: 21719508.
4)

Redhu R, Nadkarni T, Mahesh R. Diabetes insipidus associated with a thickened pituitary stalk in a case of Langerhans Cell Histiocytosis. J Pediatr Neurosci. 2011 Jan;6(1):62-4. doi: 10.4103/1817-1745.84412. PubMed PMID: 21977093; PubMed Central PMCID: PMC3173920.
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