Clinically nonfunctioning pituitary adenoma treatment

see also Recurrent clinically nonfunctioning pituitary adenoma treatment.

see Clinically nonfunctioning pituitary adenoma surgery.

● Medical management: reported tumor response rates using dopamine agonists (e.g. Bromocriptine) in 0–60% of cases, somatostatin analogs (e.g. Octreotide) in 12–40%, and combination therapy in 60% 1). These agents are therefore not recommended as a primary treatment due to lack of a significant and consistent response 2).

● XRT: studies have not shown equivalence or superiority of XRT as primary management compared to surgical management. XRT has been demonstrated to be an effective adjunctive therapy for post-op residual tumor or recurrence

● Natural history: reports of management with observation only are rare. Two studies showed tumor progression in 40–50%, and 21–28% required surgery 3) 4)

Observation only is not recommended for symptomatic NFPAs 5).

For asymptomatic microadenomas (< 1 cm dia), recommend: F/U pituitary MRI at years 1, 2, 5 and ± 10 (can stop F/U after 10 and possibly 5 years if no growth). For tumors > 1 cm, recommend: check visual fields, pituitary bloodwork (to R/O pituitary insuffi- ciency) and pituitary MRI at years 0.5, 1, 2 & 5, and any time symptoms develop.

Rarely, a non-functional tumor may secrete gonadotropins (FSH, LH). This does not produce a clinical syndrome. Normal and neoplastic pituitary gonadotrophs have gonadotropin-releasing hormone (GnRH) receptors and may respond to long-acting GnRH agonists (by down-regulating receptors) or GnRH antagonists, but significant reductions in tumor size do not occur.

Post treatment follow-up

Due to the lack of active hormonal products that can be followed with serial lab tests, follow-up relies primarily on serial imaging and monitoring for signs of mass effect from growing tumors (e.g. increasing visual field defects).

Level III 6)

1. T1WI fat sat & T2WI MRI should be included in imaging of NFPAs after surgery or XRT

2. long-term surveillance for tumor regrowth or recurrence is recommended

3. patients with radiologically-proven gross total resection of NFPA require less frequent monitoring than those with subtotal resection

4. the first post-op imaging should be obtained 3–4 months post-op


1. there is insufficient evidence to make recommendations for frequency of imaging or length of surveillance after surgery or XRT for NFPAs

2. there is insufficient evidence to make recommendations for the timing of the first post-XRT imaging

Level III 8)

1. evaluation for endocrinologic pituitary dysfunction is recommended after surgery and/or XRT for NFPAs

2. post-op adrenal function evaluation is recommended on post-op day 2, week 6, and 12 months

Transsphenoidal surgery is the treatment of choice in NFMA patients with visual field defects.

The aim of treatment in these patients is to control tumor and also to improve and protect its visual function. However in many patients, pituitary dysfunction recovery cannot happen, thus, the transsphenoidal surgery is considered for restoration of visual function, rather than pituitary function 9)

However, most endocrinologists and neurosurgeons probably agree that local tumor control is also an indication for surgery. Macroadenomas elevating the chiasm would be considered an indication for surgery in many centers, even if there are no visual field defects 10).

The 'watch and wait' policy seems reasonable for microadenomas but is probably not a safe approach for macroadenomas, which appear to have a significant growth potential; in these cases, given the lack of established medical treatment, the decision for surgical intervention should balance the presence of significant comorbidities and the anaesthetic/peri-operative risks at presentation against the probability of tumour enlargement and its consequences, as well as the possible loss of advantages associated with early operation 11)

Treatment options for nonfunctioning pituitary adenomas (NFPAs) include active surveillance, surgical resection, and radiotherapy. Pituitary surgery is currently recommended as first-line treatment in patients with visual impairment due to adenomas compressing the optic nerves or chiasma. Radiotherapy is reserved for large tumor remnants or tumor recurrence following one or more surgical attempts. There is no consensus of optimal pre-, peri-, and postoperative management such as timing, frequency, and duration of endocrine, radiologic, and ophthalmologic assessments as well as management of smaller tumor remnants or tumor recurrence.

In clinical practice, there is a great variation in the treatment and follow-up of patients with NFPAs. We have, based on available data, suggested an optimal management strategy for patients with NFPAs in relation to pituitary surgery. Prospective trials oriented at drawing up strategies for the management of NFPAs are needed 12).

The management of clinically nonfunctioning pituitary adenoma invading the cavernous sinus (CS) is currently a balancing act between the surgical decompression of neural structures, radiotherapy and a wait-and-see policy.

Those tumors that require treatment are generally macroadenomas.

Therapy is directed at eliminating mass effect and correcting hypopituitarism. 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.

see Cabergoline for clinically nonfunctioning pituitary adenoma.

Silent adenomas that cause neurologic deficits require transsphenoidal surgery, but those that do not can be followed by MRI. Residual or recurrent disease is treated by radiation therapy, which is usually effective in preventing further growth but results in hormonal deficiencies in about half of patients. Dopamine agonists and somatostatin analogs are usually ineffective, but occasionally have been associated with reduced adenoma size 13).

Clinically nonfunctioning pituitary adenoma radiosurgery

1) , 2) , 5)
Lucas JW, Bodach ME, Tumialan LM, et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Primary Management of Patients With Nonfunctioning Pituitary Adenomas. Neurosurgery. 2016; 79:E533–E535
Dekkers OM, Hammer S, de Keizer RJ, et al. The natural course of non-functioning pituitary macroadenomas. Eur J Endocrinol. 2007; 156:217–224
Arita K, Tominaga A, Sugiyama K, et al. Natural course of incidentally found nonfunctioning pituitary adenoma, with special reference to pituitary apoplexy during follow-up examination. J Neurosurg. 2006; 104:884–891
6) , 7) , 8)
Ziu M, Dunn IF, Hess C, et al. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Posttreatment Follow- up Evaluation of Patients With Nonfunctioning Pituitary Adenomas. Neurosurgery. 2016; 79:E541– E543
Dekkers OM, Pereira AM, Romijn JA. Treatment and Follow-Up of Clinically Nonfunctioning. Pituitary Macroadenomas. J Clin Endocrinol Metab. 2008;93:3717–26
Dekkers OM, Hammer S, de Keizer RJ, Roelfsema F, Schutte PJ, Smit JW, Romijn JA, Pereira AM. The natural course of non-functioning pituitary macroadenomas. Eur J Endocrinol. 2007 Feb;156(2):217-24. PubMed PMID: 17287411.
Karavitaki N, Collison K, Halliday J, et al. What is the natural history of nonoperated nonfunctioning pituitary adenomas. Clin Endocrinol (Oxf) 2007;67:938–43.
Esposito D, Olsson DS, Ragnarsson O, Buchfelder M, Skoglund T, Johannsson G. Non-functioning pituitary adenomas: indications for pituitary surgery and post-surgical management. Pituitary. 2019 Apr 22. doi: 10.1007/s11102-019-00960-0. [Epub ahead of print] Review. PubMed PMID: 31011999.
Mayson SE, Snyder PJ. Silent (clinically nonfunctioning) pituitary adenomas. J Neurooncol. 2014 May;117(3):429-36. doi: 10.1007/s11060-014-1425-2. Epub 2014 Mar 28. PubMed PMID: 24676675.
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