Received: 2 January 2024 Revised: 30 May 2024 Accepted: 16 June 2024

DOI: 10.1111/jne.13427

REVIEW ARTICLE

Advancement in perioperative management of pituitary

adenomas—Current concepts and best practices

Ismat Shafiq 1 | Zoë R. Williams 2 | G. Edward Vates 3

1
Division of Endocrinology, Diabetes, and
Metabolism, University of Rochester School of Abstract
Medicine and Dentistry, Rochester, New
Pituitary adenomas are very common representing 18.1% of all brain tumors and
York, USA
2
Department of Ophthalmology, University of are the second most common brain pathology. Transsphenoidal surgery is the
Rochester School of Medicine and Dentistry, mainstay of treatment for all pituitary adenomas except for prolactinomas which
Rochester, New York, USA
3
are primarily treated medically with dopamine agonists. A thorough endocrine
Department of Neurosurgery, University of
Rochester Medical Center, Rochester, New evaluation of pituitary adenoma preoperatively is crucial to identify hormonal com-
York, USA
promise caused by the large sellar mass, identifying prolactin-producing tumors
Correspondence and comorbidities associated with Cushing and acromegaly to improve patient care
Ismat Shafiq, Division of Endocrinology, and outcome. Transsphenoidal surgery is relatively safe in the hands of experi-
Diabetes, and Metabolism, University of
Rochester School of Medicine and Dentistry, enced surgeons, but still carries a substantial risk of causing hypopituitarism that
601 Elmwood Ave/Box 693, Rochester, NY required close follow-up in the immediate postoperative period to decrease mor-
14642, USA.
Email: [email protected] tality. A multidisciplinary team approach with endocrinologists, ophthalmologists,
and neurosurgeons is the cornerstone in the perioperative management of pitui-
tary adenomas.

KEYWORDS
cortisol/corticosterone, perioperative, pituitary adenomas, prolactin, transphenoidal surgery

1 | I N T RO DU CT I O N an endocrinologist, neurosurgeon, otolaryngologist, and ophthal-

mologist.5 It's important to acknowledge that there exist substan-
Pituitary adenomas, benign growths originating in the pituitary gland, tial institutional variations in the peri- and postoperative,
are mostly found incidentally on imaging studies. Incidental pituitary management of pituitary adenomas.3,5–11 In this review, we delve
adenomas, encountered in roughly one out of 10 pituitary glands, are into the peri-and postoperative care of pituitary adenomas, cover-
typically small, clinically inconsequential, and often necessitate no ing endocrine, ophthalmologic, and surgical aspects, drawing both
therapeutic intervention.1 In contrast, clinically relevant pituitary ade- from our center's practices and insights gleaned from literature.
nomas presenting with mass effect or hormonal deficiencies and Additionally, we highlight key management consideration in func-
excess, represent a distinct medical challenge. The clinically relevant tioning adenomas. The literature search aim to identify studies
pituitary adenoma prevalence ranges from 3.9 to 7.4 cases per with focusing on perioperative management including endocrine,
100,000 per year according to population-based studies.1–3 In the surgical, and ophthalmologic aspects. An initial PubMed search
United States, the Center Brain Tumor Registry reported pituitary and was conducted with "Pituitary Neoplasms" and "Preoperative
craniopharyngeal duct tumors representing 18.1% of all brain tumors, Care" as initial Medical Subject Heading (MeSH) terms. Additional
representing the second most common brain pathology.4 Among the MeSH terms included "Adenoma" AND "Practice Guidelines" sup-
therapeutic modalities available, transsphenoidal surgery stands as the plemented with text-words such as “nonfunctioning-pituitary-
primary treatment approach for most clinically relevant pituitary adenoma,” “Cushing disease,” “acromegaly,” “prolactinoma”
tumors. “pituitary-neoplasm,” “pituitary-adenoma,” “pituitary-tumor,”
Successful surgical intervention in pituitary adenomas hinges “pituitary-surgery,” “preoperative-assessment” and “surgical-
on a multidisciplinary approach that incorporates the expertise of management.”

J Neuroendocrinol. 2024;36:e13427. wileyonlinelibrary.com/journal/jne © 2024 British Society for Neuroendocrinology. 1 of 12

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1.1 | Preoperative assessment and management hyperprolactinemia can also be seen due to stalk effect and in some
cases, there can be overlap between these entities.12,14 Input from an
The symptoms of pituitary adenomas are related to the “size” and endocrinologist can be helpful is there is question about prolactin
“functional status.” Pituitary microadenomas measure less than hypersecretion vs. stalk effect.
10 mm, macroadenomas are greater than or equal to 10 mm and giant Assessing for adrenal insufficiency (AI) is of utmost importance
tumors surpass 40 mm in size3 (Figure 1). Functional pituitary adeno- with morning serum cortisol serving as a reliable marker of
mas produce hormones in excessive amounts including prolactin assessment.7,9,18–22 In selected cases, a cosyntropin-stimulation test
(Prolactinoma), growth hormone (Acromegaly), adrenocorticotropin (CST) may be necessary for proper evaluation.18 It is crucial to exer-
(Cushing disease), and in rare cases thyroid stimulating hormone cise clinical judgment when diagnosing AI, as falsely reassuring cortisol
(TSHoma), and gonadotropins (Gonadotropinomas). About 40% of result can occur, particularly in cases with recent-onset secondary
2
pituitary adenomas are non-functional. Endoscopic transsphenoidal AI. Patient with normal serum cortisol and or CST, does not require
surgery is the cornerstone treatment for functioning pituitary adeno- glucocorticoid (GC) treatment peri-operatively.7,9,23 All patients with
mas except prolactinomas, non-functioning adenomas with visual confirmed adrenal insufficiency should receive GC replacement pre-
compromise or optic chiasm compression and/or pituitary apoplexy.3 operatively and stress-dose GC during surgery.7,18 In cases where
The preoperative assessment requires a collaborative effort patients exhibit borderline serum cortisol level, there should be low
involving an endocrinologist for hormonal evaluation, a surgeon for threshold of initiating treatment with GC. At our pituitary center, we
radiological imaging review, and an ophthalmologist to assess visual adopt a cortisol cutoff of 10 μg/dL along with clinical judgement to
compromise. determine the need for GC treatment. Preoperative CSTs are sel-
domly performed. Instead, we opt to treat patients with borderline
cortisol levels with GC. The choice of CG treatment is either hydro-
1.1.1 | Preoperative endocrine evaluation cortisone or prednisone, with a typical hydrocortisone dose ranging in
15–20 mg, administered in divided doses.18,19,21,24,25 Further, patients
Assessment of hormonal excess and deficiencies is recommended in with diagnosed AI, will require perioperative stress-dose GC. The dos-
all patients with pituitary adenomas regardless of symptoms.3,5,7,12–18 ing and timings of stress-dose GC can vary significantly at the time of
Table 1 illustrates the tests that need to be obtained preoperatively in pituitary surgery. The Endocrine Society recommendation is to use
patients with diagnosed pituitary adenomas. hydrocortisone 50–100 mg intravenously at the time of incision fol-
In the evaluation of pituitary macroadenomas, assessing the pro- lowed by 25–50 mg hydrocortisone orally or intravenously every 6 h
lactin level is crucial. Effective management of prolactinomas primarily with a plan for a quick taper depending on recovery.3,18,26 Some varia-
relies on medical treatment with dopamine agonists. Therefore, it is tions in practice include the use of dexamethasone as a stress dose
imperative to assess serum prolactin levels in all individuals diagnosed preoperatively. Inder et al suggested the use of dexamethasone 4 mg
with pituitary adenomas, as these levels can significantly influence followed by a quick taper as stress-dose GC since secondary AI
treatment decisions.3,12 In most cases, there exists a correlation patients have normal mineralocorticoid function.9 It is important to
between adenoma size and prolactin level, with levels exceeding note that there is no randomized control trial directly comparing the
250 ng/mL typically indicative of a macroadenoma, however use of intraoperative stress dose hydrocortisone with dexamethasone

F I G U R E 1 Classification of pituitary adenomas based on size: Figure 1A (left) T 1 weighted MRI scans coronal view with a microadenoma,
(middle) T 1 weighted MRI head sagittal view showing a macroadenoma, (right) T 1 weighted MRI scans sagittal view of a giant macroadenoma.
 13652826, 2024, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jne.13427 by UFTM - Universidade Federal do Triangulo Mineiro, Wiley Online Library on [07/04/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SHAFIQ ET AL. 3 of 12

TABLE 1 Preoperative hormonal assessment of pituitary adenomas.

Pituitary axis Tests Comments

Prolactin Axis Prolactin • Avoid exercise and nipple stimulation 30 min before exercise
• Prolactin levels correlate with the size of adenoma, prolactin levels exceeding 250 ng/mL
typically indicative of a macroadenoma.
• There may be discrepancies in prolactin level and size in the setting of cystic prolactinoma
and drugs like risperidone and metoclopramide.
• Consider Endocrinology evaluation for further work up of hyperprolactinemia if needed
Adrenal Axis AM cortisol • A morning serum cortisol concentration between 8 and 15 μg/dL suggests an intact
Dynamic testing (CST) if HPA axis
needed • Obtain CST if AM cortisol 3–8 μg/dL
Salivary cortisol or 24-h urine • AI is confirmed if AM cortisol is 3 μg/dL and or if CST is abnormal
cortisol or DST • A normal CST result is defined by an increase in cortisol greater than 18 μg/dL after an
injection of 250 mcg of an ACTH analog
• Treat with GC preoperatively if AI is confirmed or suspected
Hydrocortisone 15 mg in divided doses or prednisone 5 mg daily
• Stress dose GC is needed preoperatively in patients with diagnosed AI
Hydrocortisone 50–100 mg IV at anesthesia induction followed by a quick taper
Growth hormone IGF-1 • Normally elevated IGF-1 in adolescence and pregnancy
axis • Falsely low IGF-1 can be seen with liver/renal failures, uncontrolled diabetes,
hypothyroidism, malnutrition, and oral contraceptive use.
• A mildly elevated IGF-1 or equivocal test should be confirmed with a glucose
suppression test
Thyroid axis TSH and free T4 • A low free T4 level with inappropriately normal or low TSH is diagnostic for central
hypothyroidism
• Treat central hypothyroidism with levothyroxine preoperatively
• Always rule out AI prior to initiating levothyroxine.
• TSH is not reliable, always follow free T4 levels. Target free T4 level in the mid to high
normal range.
Gonadal Axis LH, and FSH in both sexes The assessment of pituitary-gonadal function is contingent on the patient's gender and age
Serum Testosterone in males • Always check testosterone via LCMS in the morning in males
Serum Estradiol in • No need for biochemical testing in a female patient with a normal menstrual cycle
premenopausal female • In selected patients, a progesterone challenge test may be employed to confirm the
presence of estrogen deficiency
• For postmenopausal females, assessing serum FSH levels can aid in delineating pituitary
insufficiency
• No need to treat preoperatively.
Fluid and Serum sodium • If patient symptomatic with polyuria/polydipsia and has high normal or elevated serum
electrolyte sodium, check urine osmolarity
imbalance • Treat with desmopressin if needed

Abbreviations: AI, adrenal insufficiency; CST, cosyntropin stim test; DST, dexamethasone suppression test; GC, glucocorticoids; LCMS, liquid
chromatography mass spectrometry.

in patients undergoing TSS for pituitary adenomas. Thus, it is advis- Of note, thyroid hormone replacement should always be started after
able to adhere to the current best practices and guidelines to optimize treating adrenal insufficiency to prevent adrenal crisis.
patient outcomes until further evidence emerges through comparative Arginine vasopressin deficiency (AVP-D) is a relatively infrequent
studies. in patients with pituitary adenoma.33 AVP-D presence, particularly in
Central hypothyroidism is proactively treated with thyroid the absence of significant suprasellar involvement, may serve as a
replacement to prevent potential cardiac and respiratory compromise, diagnostic clue pointing towards conditions other than adenomas,
3,26–28
postoperative ileus, and hyponatremia. Some experts propose a such as lymphocytic hypophysitis or other infiltrative disease. AVP-D
perioperative levothyroxine regimen tailored to the severity of hypo- becomes a suspected diagnosis when there is inability to maximally
thyroidism as studies have not demonstrated significant differences in concentrate urine in the presence of elevated serum osmolality. Diag-
post-surgical mortality and cardiovascular outcomes in cases of mild nostic lab criteria may include serum sodium concentration is at or
29–32
to moderate untreated hypothyroidism. It is essential to empha- greater than 145 mEq/L (≥145 mmol/L) concurrently with urine
size, that due to limited data available, the decision to treat patients osmolality less than 100 mOsm/kg.33 In the management of such
with central hypothyroidism should be per the established guidelines. cases, preoperative medical intervention with desmopressin may be
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4 of 12 SHAFIQ ET AL.

contemplated as a potential strategy to alleviate symptoms in care- the contralateral eye.49 The most common visual field pattern from
fully selected patients.34 pituitary adenomas is bitemporal hemianopia which may be complete
Perioperative assessment of systemic complications of acromeg- or incomplete usually with a denser superotemporal than inferotem-
aly and Cushing disease is paramount to decrease mortality. Both con- poral component due to differential compression of the chiasm from
ditions are linked with various comorbidities including hypertension below.49 Rarely, posterior chiasmal compression causes a bitemporal
and hyperlipidemia, diabetes, and obstructive sleep apnea hemianopic scotoma due to the more posterior location of the macu-
17,35–40
(OSA). Assessment and treatment of theses comorbidities lar fibers crossing through the chiasm.49 Furthermore, in the setting of
should not be delayed, and appropriate treatment should be initiated a post-fixed chiasm, there can be bilateral optic neuropathy rather
in conjunction with other healthcare teams.35 than a chiasmal visual field defect.50 With a pre-fixed chiasm, there
Cushing disease, leading cause of endogenous hypercortisolemia, can instead be an optic tract syndrome with homonymous
entails a range of comorbidities encompassing cardiovascular, throm- hemianopia.50
41,42
boembolic, metabolic, infectious, and psychiatric disorders. Cush- There are also several mechanisms by which pituitary adenomas
ing disease patients face an elevated susceptibility to infection and can cause efferent disorders including diplopia. With an extension to
venous thromboembolism (VTE), especially post-surgery due to the cavernous sinus, pituitary adenomas can cause cranial nerves III,
35,43–45
decreased cortisol levels. Thromboprophylaxis is crucial, IV, or VI nerve palsies. A pituitary adenoma with chiasmal compres-
though guidelines regarding timing, type and duration are lacking.46,47 sion producing complete bitemporal hemianopia can also cause diplo-
The Pituitary Society recommends commencing thromboprophylaxis pia in the setting of a pre-existing latent ocular misalignment (phoria)
agents a few days to 1–2 weeks before surgery, with continued due to the hemifield slide phenomenon, in which loss of overlapping
administration for a duration of 2–6 weeks or potentially longer after visual fields decompensates a patient's fusional capacity.49 Rarely a
35,41
surgery. Additionally, it is advisable to promote mechanical antith- large pituitary adenoma with chiasmal compression can cause pendu-
rombotic practices like the use of compression stockings and early lar see-saw nystagmus, in which one eye elevates and intorts while
ambulation.41 Pneumocystis jirovecii pneumonia (PJP), possess a sig- the other eye depresses and extorts in a cyclic alternating pattern.49
nificant risk, particularly in those with profoundly elevated cortisol Pre-operative assessment of peripapillary optical coherence
levels with urine-free cortisol measurement exceeding 20 times the tomography of the retinal nerve fiber layer (OCT RNFL) to evaluate
upper limit of normal.35,43,48 While official guidelines are lacking, s for ganglion cell complex or axonal loss has predictive value for post-
prophylactic treatment with trimethoprim-sulfamethoxazole for indi- operative visual recovery.51 It has been established that a preopera-
35
viduals with severe hypercortisolemia can be considered. tive average peripapillary RNFL of <75 microns predicts a guarded
Patients with acromegaly often contend with obstructive sleep prognosis for full visual recovery, whereas an RNFL of ≥75 microns
apnea (OSA) and structural changes in their airways caused by soft tis- predicts an excellent visual recovery regardless of the density of the
sue hypertrophy and alterations in bone structure. These factors can pre-operative visual field loss.51 With chronic chiasmal compression,
present challenges when managing the airway during pituitary sur- the optic nerves develop thinning of the nasal retinal nerve fibers in
gery.39 To ensure a successful surgical outcome in such cases, it is cru- the papillomacular bundle (temporal to the disc) and directing entering
cial to conduct thorough pre-operative evaluations by the nasal aspect of the disc which causes a characteristic bow-tie or
anesthesiologists and ear, nose, and throat (ENT) specialists. The rou- band atrophy of optic disc pallor.49 In a patient with nasal ganglion cell
tine preoperative use of somatostatin analogues in acromegaly is a complex loss by OCT, a compressive pituitary lesion should be sus-
topic of debate, as current guidelines do not advocate for its wide- pected.52 More recently a case–control study of OCTA (optical coher-
13
spread application. ence tomography angiography) in patients with pituitary adenomas
suggested preserved radial peripapillary capillary density may be a
better predictor of visual field recovery 1-week post-decompression
1.1.2 | Preoperative ophthalmological evaluation than retinal nerve fiber layer thickness; however, this study had some
limitations including small sample size53 Currently OCTA is not rou-
A complete assessment of the afferent visual pathway including tinely performed in the evaluation of patients with pituitary adeno-
best-corrected visual acuity, color vision, pupillary assessment, for- mas. It is not widely available in clinical practice and has some
mal visual field testing via automated perimetry, optical coherence technical limitations. In patients presenting with both afferent and
tomography, and optic disc appearance is essential in patients with efferent visual deficits, headaches, nausea/emesis, and mental status
pituitary lesions to determine the visual significance of the changes, pituitary apoplexy must be considered. The most typical
3,49
pituitary adenoma. efferent visual disorder of pituitary apoplexy is cranial nerve III palsy.
Several patterns of peripheral vision loss have been described
depending on the location of the pituitary tumor in relation to the
optic chiasm. A junctional scotoma occurs when the pituitary tumor is 1.1.3 | Preoperative surgical evaluation
anterior to the body of the chiasm and impinges on the distal optic
nerve in one eye as well as the inferonasal crossing fibers from the Magnetic resonance imaging (MRI) is the mainstay imaging modality in
contralateral pre-chiasmal optic nerve.49 This causes optic neuropathy evaluating pituitary adenomas and adjacent structures.54,55 A typical
in one eye and an asymptomatic superotemporal visual field defect in MRI with pituitary protocol is with high resolution at 1.5–3 Tesla and
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SHAFIQ ET AL. 5 of 12

includes coronal and sagittal imaging along with dynamic post- experience.66–68 Surprisingly, factors such as age, sex, tumor size, or
contrast images. Identification of the normal pituitary gland, recogniz- extent of resection have not been consistently shown to predict the
ing the chiasm, and detecting the extent of parasellar invasion by development of postoperative hormonal deficiencies.68,69 Jehangiri
using the Knosp grading system; can help in estimating the extent of et al. reported new postoperative deficits in 14% of patients after
cure from surgical resection.56 If MRI cannot be obtained due to medi- transsphenoidal surgery, with ACTH deficiency at 6%.68 With such a
cal reasons and or is contraindicated due to the use of metallic low postoperative risk of developing AI, and to avoid unnecessary GC
implants or devices, then computed tomography (CT) angiography use, several “steroid-sparing protocols” have been introduced over
allows for an appreciation of the anatomy of the internal carotid arter- the last two decades.9,70,71 These protocols, although numerous and
ies and the cavernous sinuses, which can often provide an indirect institution-specific, typically revolve around morning cortisol
understanding of pituitary gland and tumor anatomy.55,57,58 CT angi- levels.18,21,70–73 In cases where morning cortisol levels are in the nor-
ography also provides “bone windows” which provide an expanded mal range, GC treatment can be withheld with close observation and
understanding of the sellar anatomy, which can also be affected by a morning cortisol levels reevaluated in 1–2 weeks.70,71 Alternatively,
tumor. CT angiography is also, by definition, a pre-and post-contrast some practices opt to administer intra-operative and post-operative
study, which allows for pre- and post-contrast assessment of the nor- GC with a quick taper.11,74 A recent study by Alexander et al reports
55,57
mal pituitary gland and any tumor. no difference in outcome whether the patient received or did not
Pituitary surgery has also evolved and currently, most of the pitui- receive postoperative glucocorticoids.75 As there is no overarching
tary adenomas are resected via the endoscopic endonasal transsphe- consensus on the best approach, clinical judgment and close monitor-
noidal approach.59 Fewer than 5% of patients undergo microscopic ing for signs and symptoms of AI should be practiced with judicious
transsphenoidal surgery in our practice; typically, the microscope is GC usage. Also, the postoperative cortisol may be challenging to inter-
used in emergency cases when coordination with the surgical endo- pret with dexamethasone use for anesthesia induction. In our center,
scopic team would result in a delay of care. In a recent meta-analysis, we have implemented a steroid-sparing protocol since 2015, initially
the endoscopic approach has been shown to provide better visualiza- employing a morning cortisol cutoff of 14 μg/dL. Subsequently, we
tion and gross total resection of the pituitary tumor as compared to have refined our protocol and now employ a morning cortisol cutoff
the microscopic approach.60 The endoscopic approach is always of 10 μg/dL.71 In cases where the post-operative cortisol exceeds
assisted by an experienced otolaryngologist. Preoperative CT of the 10 μg/dL, GC treatment is typically not administered but the decision
nasal area in patients undergoing TSS (both endoscopic and micro- is guided by clinical judgment. However, if the morning cortisol is still
scopic approaches) can identify nasal anatomy as well as the bony below 10 μg/dL, patients are discharged on GC treatment. Subse-
landmarks of the sella, the tuberculum sella, the clivus, and the quently, we then reevaluate morning cortisol after a week, if cortisol
bony limits of the cavernous sinuses including the carotid canal and stays low, patients are continued on GC treatment. A cosyntropin stim
the optic-carotid recess.61–63 test is performed at 3 months for assessment of the HPA-axis in these
In patients with large tumors, the CT is helpful to recognize the cases71 (Figure 2).
dehiscence of the sellar floor. In patients with microadenomas, under-
standing the distance between the internal carotid arteries and the Post-operative fluid and electrolytes management
septations within the sphenoid sinus (and their relationships to Sodium fluctuations are seen postoperatively after TSS due to over or
the anatomic midline and the carotid canals) is important for recogniz- under secretion of the “Arginine Vasopressin (AVP).33 Post-
ing the safe entry point into the sella and for avoiding injury to the operative AVP-D occurs in approximately 25%–30% of patients, pri-
carotid arteries (a catastrophic possibility that is best avoided by marily due traction of the pituitary stalk leading to decrease in AVP
understanding the anatomy).61,63–65 While nasal CT is not routinely release.76 Symptoms include increased thirst with fluid intake >3 L/
obtained during preoperative assessment of pituitary surgery, studies day and polyuria with urine output >50 mL/kg body weight/24 h
have shown that identifying the nasal anatomy via CT can reduce although various patterns of urine output and electrolyte imbalance
postoperative complications.63,65 In our practice, the maxillofacial CT can occur.33 Other potential contributors to postoperative polyuria
data is used in the frameless stereotactic navigation system to provide are excessive preoperative intravenous fluid administration and a
intra-operative guidance to both the ENT surgeon and the decrease in GH levels, particularly in patients with acromegaly.
neurosurgeon. Patients with intact thirst mechanisms typically have the capacity to
compensate for the water loss and maintain a normal sodium level.
High normal sodium or hypernatremia is seen if there is an increase in
1.2 | Postoperative assessment and management water loss with inappropriate compensation. Therefore, close clinical
monitoring of thirst, fluid intake, urine output and plasma and urine
1.2.1 | Post-operative endocrine evaluation osmolarity is essential. While administrating DDAVP to alleviate
symptoms is reasonable, scheduled use of DDAVP should be avoided
Post-operative adrenal axis management due to the associated risk of hyponatremia.18,33,34,76,77 AVP-D follow-
The risk of developing new postoperative pituitary hormonal deficien- ing surgery is mostly transient but can be permanent, which is
cies varies, primarily depending on the neurosurgeon's observed in about 2% of patients after TSS. At our practice, we closely
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6 of 12 SHAFIQ ET AL.

F I G U R E 2 Postoperative assessment of HPA axis in Non-functioning pituitary adenoma and Cushing disease based on our center experience.
AI, adrenal insufficiency; GC, glucocorticoids; GWS, glucocorticoid withdrawal syndrome; HPA, hypothalamic pituitary adrenal axis; POD,
postoperative day.

monitor urine output after surgery. A Urine output >200 cc/h Other post-operative hormonal assessment
prompts checking serum sodium and urine osmolarity/specific gravity. The assessment of other pituitary hormones after surgery is impor-
If the patient is diagnosed with AVP-D, a single dose of desmopressin tant. The half-life of free T4 is approximately a week. Thyroid
(DDAVP) 0.5–2 mcg intravenously/ subcutaneously or DDAVP 0.1 blood work is checked at 6–12 weeks postoperatively in patients
orally is given to alleviate symptoms. Our goal is to use the lowest with intact preoperative thyroid function.7,18 Others have recom-
possible dosage of DDAVP while maintaining a serum sodium level mended checking thyroid blood work within a week of surgery.74
above 140 mEq/L (>140 mmol/L), thereby minimizing the risk of iat- The assessment of the hypothalamic pituitary thyroid axis is chal-
rogenic hyponatremia. lenging if the patients are already on thyroid hormone replacement
The hyponatremia with SIADH is due to the excess release of preoperatively. At our practice, we adhere to the schedule of
AVP stemming from degenerating axon terminals with an incidence checking thyroid function at 2 and 12 weeks postoperatively. If a
ranging from approximately 1.8%–25%.78–83 SIADH generally occurs patient is already on levothyroxine preoperatively, the decision to
5–7 days after surgery and lasts up to 14 days.34,76 In most instances, re-assess the thyroid axis typically hinges on the recovery of the
cases of SIADH-induced hyponatremia are mild, characterized by other axis at 12 weeks.
serum sodium 130–135 mmol/L. Such cases can be effectively man- In the immediate postoperative phase, the gonadal function can
aged with fluid restriction in the outpatient setting.76 The manage- be suppressed due to stress or steroid use. The current guidelines rec-
ment of severe and symptomatic hyponatremia requires hospital ommend assessing for gonadal function at 6–12 weeks after sur-
admission and treatment with fluid restriction, sodium tablets, and or gery.18 At our center, we generally check gonadal function at
hypertonic saline.76 A recent meta-analysis examined the role of post- 12 weeks.
operative fluid restriction in preventing severe hyponatremia and Assessing for GH deficiency is not a priority in the immediate
readmission to the hospital.84 The findings indicated a noticeable postoperative period. The current guidelines recommend checking
reduction in hospital readmission rates among patients subjected to IGF-1 at 6–12 weeks postoperatively.7,18 At our practice, we check
fluid restriction, with only a 1.3% readmission rate compared to 6% in IGF-1 at 12 weeks.
the control group. While it's important to acknowledge the variability
in fluid restriction protocols, the authors suggested that fluid restric- Functional adenomas post-operative assessment
tion of 1 L on POD 4–8 can prevent 100% hyponatremia-related hos- Prolactinomas: Prolactinomas are primarily treated medically with
78,81,84
pital re-admission. In our current clinical practice, we typically dopamine agonists (DA).12 Surgery is reserved for patients resistant to
discharge patients with instructions to drink according to their thirst, DA and or intolerant to DA. Post-operative morning prolactin levels
as opposed to imposing rigid fluid restrictions (Figure 3). can be measured to predict remission, however data is limited on the
 13652826, 2024, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jne.13427 by UFTM - Universidade Federal do Triangulo Mineiro, Wiley Online Library on [07/04/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SHAFIQ ET AL. 7 of 12

F I G U R E 3 Monitoring and AVP-D

treatment water and electrolyte
disorder after transsphenoidal
surgery. AVP-D: Arginine AVP AVP
vasopressin defeciency SIADH:
Syndrome of inappropraite anti-
diuretic hormone, Labs* serum
sodium, serum osmolarity, urine
osmolarity/urine specific gravity.

use of post-operative prolactin use and further evidence is needed to insufficiency (AI) like nausea, vomiting, and hypotension. In such
identify the prolactin level to predict remission.85,86 cases, the serum cortisol levels should be monitored every 6 h.41,93
Acromegaly: Published data showed remission rate of up to 90% Patients with serum morning cortisol >10 μg/dL should be monitored
in patients with microadenoma and 50%–60% in patient with macroa- closely in the outpatient setting. In rare circumstances delayed remis-
denomas.13,15,16 In patients with acromegaly, there is an increase in sion can be seen, thus it is paramount to educate the patient on the
fluid retention of up to 25% due to an increase in epithelial sodium symptoms of AI and to check morning cortisol periodically.94
channel activity. 87
Significant diuresis is observed in the immediate The GC treatment is started when the cortisol level is <5 μg/dL
postoperative periods with a sudden decrease in GH levels.88,89 Post- post-operatively, The dosing and type of GC treatment varies among
operative morning GH levels can serve as predictor of long-term different practices. The common recommendation is to start with a
remission, although the sensitivity and specificity of this measures relatively high-dose GC with gradual withdrawal to avoid glucocorti-
90,91
varies across different studies. Some authors suggests that a coid withdrawal syndrome (GWS) in patients accustomed to supraphysio-
post-operative GH level of <1.5 μg/L can predict remission in >50% logic GC levels in Cushing disease.41,42,93 This typically involves
17,91
of patients. It is important to note, that GH/IGF-1 levels post- initiating hydrocortisone 30–60 mg or prednisone 10–20 mg in
operatively may not be interpretable if somatostatin analogs were divided doses.93 In some healthcare centers, the decision to start glu-
given preoperatively. Thus, the use of postoperative GH level has not cocorticoid treatment is made when the serum morning cortisol falls
been standardized yet due to a lack of scientific evidence. Generally, between 5 and 10 μg/dL, a practical approach when extended hospi-
the IGF-1 and GH are checked at 12 weeks.13,15,17 tal stay for close monitoring is not feasible. At our institution, we initi-
Cushing disease: The remission rate for Cushing disease can range ate GC treatment when the cortisol level drops below 10 μg/dL since
from 50% to 83%, contingent on factors such as adenoma size and most of our patients are discharged within 24 h of surgery. We typi-
the surgeon's expertise.35,41,42,92 Postoperative morning serum corti- cally use hydrocortisone 30–40 mg in divided doses and decrease it
sol are commonly used to assess remission.41,42 Although, AM cortisol by 5 mg every other week until a physiologic dose of hydrocortisone
levels are useful in prognosticating remission, no single cutoff value 15 mg is achieved. In selected cases, we may use prednisone 15–
has perfect sensitivity and specificity. Defining the ideal serum corti- 20 mg with a decrease of 2.5 mg every other week until a physiologic
sol cutoff has been challenging due to varying practices and the use prednisone 5 mg is reached. Patients with cortisol level >10 μg/dL are
of perioperative cortisol-lowering medications which can interfere closely monitored and are provided with a GC prescription with
with results. A serum cortisol below 5 μg/dL post-surgery indicates a instructions to start GC if unable to promptly check blood work and
successful procedure and necessitates the initiation of GC treat- develop symptoms of AI/GWS (see Figure 2). The symptoms of GWS
ment.35,41,42 Conversely, if serum cortisol exceeds 5 ng/dL, then close include generalized body aches, muscle weakness, and fatigue with
monitoring is essential, focusing on potential symptoms of adrenal some abdominal discomfort.93,95 Managing patient expectations after
 13652826, 2024, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jne.13427 by UFTM - Universidade Federal do Triangulo Mineiro, Wiley Online Library on [07/04/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
8 of 12 SHAFIQ ET AL.

successful surgery with proper education can alleviate anxiety. Strate- that tumor growth may present with a dimming of the temporal visual
gies like maintaining healthy sleep patterns, a high-protein diet, and fields.
93
engaging in physical therapy can help mitigate GWS.
In the postoperative phase, serum ACTH can be measured to pre-
dict long-term remission. However, it is important to note that there 1.2.3 | Postoperative surgical evaluation
is limited data on ACTH as a prognostic marker. An ACTH level of
below 20 ng/L has shown promise in predicting remission, whereas Surgical complications are uncommon in the hands of experienced
higher levels may suggest persistent disease or elevated risk of pituitary surgeons.104,105 The mortality is 0.4%–0.9% with TSS
96,97
recurrence. depending on the experience of the surgeon.104 Post-operative com-
In certain centers, additional tests like 24-h urine-free cortisol plications include cerebrospinal fluid (CSF) leak, meningitis, and vascu-
and salivary cortisol are conducted immediately post-operatively to lar or neurological injury. CSF leak is reported in 0.5%–4% of patients
help define remission. However, their interpretation can be challeng- following TSS. Nasal discharge after surgery is common given the sur-
ing in the contest of GC use.98,99 There is no consensus on the utility gical corridor through the nasal passages, but the symptoms of CSF
of using these tests in the immediate postoperative period.7 leak are consistent and easy to recognize. Symptoms include clear
For patients who continue to exhibit persistently elevated serum watery nasal discharge that is elicited when the patient leans forward,
morning cortisol levels (>10 μg/dL), follow-up testing for hypercorti- sometimes headaches, and a metallic taste in the mouth. Symptoms
solemia should be scheduled within 6–12 weeks, with the timing are worse when sitting or standing. CSF leak is much more likely if
dependent on the severity of symptoms.41 In the setting of confirmed CSF was encountered during the resection of the tumor; in the
persistent hypercortisolemia, consideration should be given to further absence of CSF egress during tumor resection, the likelihood of CSF
intervention. This may include repeat TSS or explorations of alterna- leak is incredibly low but should not be ignored. CSF leak can be con-
tive options such as medical therapy, radiotherapy, or adrenalec- firmed by evaluating the fluid for beta 2 transferrin protein (a protein
tomy.41,42 The choice of intervention should be guided by the only present in CSF), but frequently the symptoms and onset of the
patient's specific clinical circumstances and the recommendations of fluid drainage within days after surgery are sufficient to warrant man-
their healthcare team. agement at the discretion of the surgeon. The best way to manage a
CSF leak is to deal with it during surgery, and many techniques exist
to address a CSF leak during surgery (this is outside the scope of this
1.2.2 | Postoperative ophthalmological evaluation review). Diamox is a diuretic that will transiently reduce CSF produc-
tion from the choroid plexus; in our experience, it has limited utility
Post-operatively, re-evaluation of the patient's afferent and efferent and can complicate electrolyte and fluid management after pituitary
visual function including formal visual field assessment should be per- surgery. If a CSF leak is of sufficient concern, it is typically managed
formed, although the ideal post-operative timing of evaluation is not by admitting the patient back to the hospital with the placement of a
well defined. There can be an immediate improvement of visual field lumbar subarachnoid drain.106 This allows the diversion of CSF and
defects with decompressive surgery but, generally, there is a contin- will almost always cause the nasal egress of CSF to cease. In our expe-
ued improvement over weeks to a few years post-operatively, with rience, lumbar drainage for 2–4 days is usually sufficient, and when
pre-operative OCT RNFL predicting the probability and timing of appropriate the drain can be clamped for 12–24 h. If the leak does
improvement.100–103 Patients with significant visual field loss at base- not recur, the drain can be removed, and the patient discharged again.
line but normal preoperative OCT RNFL have more significant visual If a CSF leak persists after a trial of lumbar drainage, then options
field recovery than patients with significant visual field loss at baseline include reoperation to address the point of leakage or placement of a
53
with thin pre-operative OCT RNFL. In the prospective study by permanent system for CSF diversion (a ventriculoperitoneal shunt or
Danesh-Meyer et al., most of the improvement in the visual field a lumboperitoneal shunt). While direct surgical repair may seem a
occurred by 6–10 weeks post decompression in patients with normal priori the preferred option, it is not always the best option, especially
pre-operative OCT RNFL; whereas, patients with thin pre-operative in patients with morbid obesity (which can elevate CSF pressures
OCT RNFL were slower to improve, with most of the improvement independent of the pituitary pathology) or in patients with variant
occurring between 10 weeks and 15 months.53 Of note, post- nasal anatomy that increases the difficulty of direct surgical repairs.
operative evaluation was not performed earlier than 6 weeks in this Olfactory dysfunction after transsphenoidal surgery is common in
study, although other studies have demonstrated some visual recov- the immediate post-operative period; this is due to congestion of the
ery by 1-week post-decompression.53 An additional study by Wang nasal passages and rarely lasts more than a few weeks after surgery.
et al. showed with normal pre-operative OCT RNFL, visual field recov- In some patients, crusting of the nasal passages after surgery can
ery is generally complete within 6 weeks; whereas with thin pre- impair olfaction, and this is why our patients are routinely evaluated
operative OCT RNFL, visual field recovery may continue for up to by our ENT surgeon 4 weeks after surgery with direct endoscopy in
103
6 months. Even patients who have excellent visual recovery with the office to assess healing of the nasal passages and to provide reas-
surgical decompression should be periodically monitored with visual surance to the patient. Permanent loss of olfaction after transsphenoi-
field testing for recurrent tumor/interval tumor growth and advised dal surgery is fortunately quite rare and most series suggest the rate
 13652826, 2024, 11, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/jne.13427 by UFTM - Universidade Federal do Triangulo Mineiro, Wiley Online Library on [07/04/2025]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SHAFIQ ET AL. 9 of 12

of anosmia 1 year after surgery of 5%107 but is of sufficient fre- 2. Daly AF, Beckers A. The epidemiology of pituitary adenomas. Endo-
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AUTHOR CONTRIBUTIONS aspects of pituitary adenoma surgery in Europe. Sci Rep. 2022;12(1):
6529.
Ismat Shafiq: Conceptualization; data curation; formal analysis; pro-
9. Inder WJ, Hunt PJ. Glucocorticoid replacement in pituitary surgery:
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Pituitary. 2008;11(4):347-351.
writing – review and editing.
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agement of patients after pituitary surgery. Ther Adv Endocrinol
ACKNOWLEDGMENTS Metab. 2017;8(3):33-48.
We would like to thank Jaimi Mclean, a Liaison Librarian at the Uni- 12. Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treat-
ment of hyperprolactinemia: an Endocrine Society clinical practice
versity of Rochester for her support.
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