Endocrine Outcomes Following Endoscopic Transsphenoidal Pituitary Surgery in Erbil, Iraq

doi:10.21203/rs.3.rs-4972082/v1

Objective

The impact of endoscopic transsphenoidal pituitary surgery (ETSs) on endocrine function is a critical concern of surgical treatment of pituitary tumors. This study evaluated post-ETSs pituitary disease control (DC), development of early and late new hormonal deficiencies, and recovery of pre-existing hormonal deficiency. Additionally, studied the preoperative factors that influence post-ETSs outcome.

Methods

A prospective cohort study conducted in neuroendocrine field in Erbil city from April 2023 to April 2024. The study included 35 patients who were assigned for ETSs after exclusion of those with prior neurosurgical intervention, radiation, or drugs affecting pituitary function. Initial clinical evaluation, endocrine tests and radiological imaging performed pre-ETSs, then at early postoperative period and later follow up scheduled at one-, three-, and six-month interval.

Results

Post-ETSs, DC achieved in 20 (57.1%) of patients. At six-month follow up, about 10/18 (55.5%) patients recovered at least one hormone postoperatively with gonadal axis was the most frequent 5 (14.3%), while new hormonal deficiencies documented in 12 (34.3%) patients, among which prolonged Diabetes insipidus (DI) was the most frequently encountered 11 (31.4%). Early post-ETSs water dysregulation significantly prolonged hospital stay (p-value 0.035). Tumor size, knops classification and surgeon experience were the main variables associated with endocrine outcome.

Conclusion

In Iraq, Erbil city, DC rate was lower than previous studies, and development of new hormonal deficiencies was higher and contributed to prolonged DI. However, a considerable number of patients had recovery of pre-existing hormonal deficiencies compared to prior studies. These findings necessitate revision of our surgical management.

Outcome

transsphenoidal surgery

endoscopic

pituitary adenoma

Iraq

Surgical treatment is well-established first-line management for most pituitary lesions to alleviate mass effect, correct hormonal hypersecretion. Additionally, immediate surgical decompression may be indicated for pituitary hemorrhage [1].

The ETSs was introduced in 1992 by Jankowski and became the preferred method for approaching pituitary and skull base tumors for its better visualization and reduced invasiveness [2].

Endocrine complications following endoscopic transsphenoidal surgery (ETSs) are a crucial consideration in patient care and management. Common endocrine complications may include water dysregulation, and anterior pituitary hormone deficiencies due to interruption of hormonal regulation, or damage to the pituitary gland and/ or neighboring structures during surgery [3]. The most important predictors of ETSs outcomes were found to be related to tumor characteristics and surgical experience [4].

In Erbil, Iraq, ETSs was recently introduced to the medical practice thus the evaluation of post-ETSs endocrine outcome is mandatory to have an insight on the current surgical performance and postoperative complications. This study would alert both endocrinologists and neurosurgeons to any potential outcome that requires timely intervention.

This study aims to evaluate endocrine outcomes post-ETSs including disease control (DC), recovery of pre-existing deficient hormones, detection of new hormonal deficiency and factors that influence these outcomes.

Study design

A longitudinal prospective cohort study conducted in neuroendocrine department of two different hospitals (Par hospital and Erbil teaching hospital) in Erbil, Iraq from April 2023 to April 2024.

Inclusion criteria

The study recruited 52 consecutive patients who were assigned for ETSs intended for therapeutic reasons. An informed written consent was taken from all patients. The study Approved by Faiha Specialized Diabetes, Endocrine and Metabolism Center (FDEMC) Ethical Committee (ref #56/35/30) on March 19, 2023, in line with the Declaration of Helsinki. Fifteen patients were lost follow up and two patients died in the early postoperative period. Ultimately 35 patients were studied.

Exclusion criteria

The study excluded any patient with previous surgical or radiation therapy for any Sellar or brain lesion. We also excluded those under hormonal replacement treatment for a primary endocrine disease, patients who were taking steroid therapy for reasons other than pituitary disease, or patients received chemotherapy or any other medical treatment known to impact pituitary function.

Surgical Team

All ETSs performed by four neurosurgeons and two otorhinolaryngologists using the standard endoscopic surgical technique described in the literatures (two surgeons/ four hands). Surgeons were categorized according to their annual surgical volume: one surgeon were conducting fewer than 10 surgeries was categorized as low-experienced, one surgeon was performing between 10 and 25 surgeries annually categorized as moderately-experienced, and two surgeons were carrying out more than 25 surgeries annually categorized as high-experienced [5].

Endocrine and neuroradiology assessment

All patients underwent pre-operative pituitary hormonal assessment as baseline then at early postoperative period and later follow up scheduled at one-, three- and six-month interval post-ETSs in the absence of indications for earlier testing.

Hormonal pituitary assessment was carried out for all patients in the fasting state. Roche Cobas 6000 analyzer (e 601 module) was used to measure serum hormones by electrochemiluminescence immunoassay kits. The normal range of hormones was set based on laboratory references and included insulin-like growth factor-1 (IGF-1) (sex and age-adjusted normal range), prolactin (male: 4-15.2 ng/ml, female 4.7–23.3 ng/ml), ACTH (7.2–63.3 pg/ml), cortisol (6.1–19.4 mcg/dl), TSH (0.27–4.2 mIU/ml), free thyroxine (FT4) (0.93–1.7 ng/dl), luteinizing hormone (LH) (male:1.7–8.6 mIU/ml, female: 2.4–58.5 mIU/ml according to menstrual cycle), follicle stimulating hormone (FSH) (male: 1.5–12.4 mIU/ml, female: 3.5–135 mIU/ml according to menstrual cycle), testosterone (in male patients) (2.8-8.0 ng/ml), and estradiol levels (in female patients) (< 5- 498 pg/ml).

Alongside, the assessment of posterior pituitary function specifically antidiuretic hormone (ADH) function involved the measurement of serum and urine osmolality using the same analyzer (c 501 module) through ion-selective electrodes and photometric tests of serum and urine electrolytes, glucose, and blood urea nitrogen then osmolalities were calculated by the analyzer software.

To evaluate secretory potential of pituitary gland further dynamic tests were done including serum GH level after oral glucose tolerance test (OGTT) (when acromegaly was suspected) (normal GH nadir: < 1 ng/ml). If Cushing’s disease was suspected, we performed serum cortisol after 1-mg overnight dexamethasone suppression test (ODST) (normal serum cortisol < 1.8 ng/dl), and 24-hour urinary cortisol (normal cortisol < 3 folds of upper normal limit, 3.5–45 µg/day), and when pituitary adenoma was less than 6 mm in size then high dose dexamethasone suppression test (suppression of cortisol by < 50% define ACTH-dependent Cushing’s disease) was also done. Further dynamic tests like Cosyntropin-stimulation test (normal cortisol response greater than 18 µg/dl after injection of 250 mcg of ACTH analogue), and clonidine stimulation test (normal peak GH > 7.5 ng/ml) was carried out to evaluate for cortisol and GH deficiency respectively [6, 7].

All patients underwent magnetic resonance imaging (MRI) with a dynamic pituitary imaging protocol preoperatively then at three-, and six-month postoperatively to determine the extent of tumor resection and posterior pituitary bright spot (PPBS) respectively, except in the presence of indications for earlier imaging. Tumor size, defined by its maximum diameter, and classified into Microadenoma (< 10 mm), Macroadenomas (10–40 mm) and giant adenoma (> 40 mm). For cavernous sinus invasion, the classification of Knosp was applied [8].

Post-ETSs monitoring for DC

The DC of NFPAs defined as gross total resection (GTR) when the postoperative imaging revealed total resection of the tumor. Subtotal resection (STR) defined as removal of more than 80% of the tumor, while partial resection (PR) defined as removal of less than 80% of the tumor [9].

In FPAs, DC defined by biochemical hormonal control as following: in acromegaly by normalization of IGF-I level and nadir GH after OGTT of less than 1 mg/L) [10]. In Cushing’s by morning serum cortisol concentration less than 5 µg/dl while withholding glucocorticoid replacement. If the morning cortisol concentration was greater than 5 µg/dl, the patient underwent ODST and/ or 24-hour urinary cortisol to confirm DC [6]. In prolactinomas, DC was defined by normalization of prolactin level [6]. In a subset of patients with FPA, we monitored the patients up to 3 months without initiating any further targeted treatment to detect late DC, if the patient underlying excess hormone remained uncontrolled at three-month, then the condition labeled uncontrolled [11].

Post-ETSs monitoring for hormonal deficiency

In the early few days post ETSs, we measured serum sodium and morning cortisol to all patients to monitor development of adrenal insufficiency, syndrome of inappropriate antidiuretic hormone (SIADH), central Diabetes insipidus (DI), or the triphasic response.

A serum morning cortisol less than 10 µg/dl was regarded as early ACTH deficiency and necessitated glucocorticoids replacement therapy, while values above 10 µg/dl was regarded as normal hypothalamic pituitary adrenal axis. Cortisol was then assessed, at one-, and six-month postoperatively after withholding hydrocortisone for 24 hours. At each time If the morning cortisol concentration remained less than 10 µg/dl, glucocorticoid replacement was continued. Cosyntropin-stimulation test performed at six-month post-ETSs if the cortisol value was less than 10 µg/dl [6].

Patients with hyponatremia (serum sodium < 135 mEq/L) have been further evaluated clinically by assessing hydration status and urine output, and by biochemical measurement of serum osmolality, urinary sodium and urine osmolality. Accordingly, SIADH was diagnosed if serum osmolality was < 275 mOsmol/kg, urine sodium > 30 mEq/L, urine osmolality > 100 mOsmol/kg, and the patient was euvolemic with normal urine output, thyroid, adrenal and renal function [12].

The central DI diagnosed after discounting further reasons of polyuria, by urine output of more than 250 mL per hour for two consecutive hours in the presence of normal or high serum sodium (> 145 mEq/L), normal or high serum osmolality and urine osmolality of less than 300 mOsmol/ kg. In addition to calculated urine osmolality, bedside urine specific gravity of less than 1.005 also used to define low urine osmolality [13]. Central DI was defined as early DI if developed at early post-ETSs, and as prolonged DI if persisted at six-month post-ETSs.

The SIADH, and central DI occurred either as isolated or as part of triphasic response. Triphasic response defined by central DI interrupted by short period of SIADH.

Definition of persistence of new hormonal deficiency and/ or recovery of previously deficient hormone based on hormonal profile at six-month post-ETSs. Deficiency of TSH defined by low FT4 with inappropriately low, normal TSH. Prolactin deficiency considered when prolactin level was less than normal reference range. Deficiency of gonadal axis defined by low testosterone (in male), or low estradiol (in female) with inappropriately low/ normal FSH/LH. Deficiency of GH assessed by clonidine stimulation test, except for those patients with three pituitary hormonal axis deficiencies, for whom IGF-1 was done initially, and if the result of IGF-1 level was normal then clonidine stimulation proceeded, otherwise if IGF-1 level was low, the patient diagnosed as GH deficiency.

Low GH, prolactin, or ACTH in patients with acromegaly, prolactinoma, or Cushing’s disease respectively were not considered as endocrinological complications but rather regarded as achievement of DC.

Statistical analysis

The data analyzed using the statistical package of social science (SPSS) software, version 26 (IBM Co., Armonk, NY, USA). Number (N), and percentage (%) used to present the frequency of pre-ETSs patients' characteristics and post-ETSs outcomes. Fisher exact test and Chi-square test used to find out the variables associated with ETSs outcomes.

Preoperative demographic characteristics

Of 35 patients assigned for ETSs, 20 (57%) were females. The majority 28 (80%) of patients aged more than 30 years old. The most frequent tumor characteristics represented by acromegaly 13 (37.1%), macroadenomas 24 (68.6%), and Knosp grade 2 (34.3%). About one half 18 (51.4%) of patients had pre-existing hormonal deficiency. The surgery was mostly performed by high- 15 (42.9%) and moderate-experienced surgeons 14 (40%) respectively [Table 1].

Post-ETSs outcome

Early in the postoperative period, most of the patients 22 (62.9%) were required hospitalization for about one to three days. Three (8.9%) patients were readmitted after initial discharge. Water dysregulation complicated hospital stay in 21 (60%) patients, with DI (either alone or as a phase of triphasic response) being the most frequent disorder 19 (54.3%). Early ACTH deficiency also encountered in 4 (11.4%) patients. Assessment of late post-ETSs outcome included: positive impact of ETSs (DC and recovery of pre-existing hormonal deficiency), and negative impact represented as persistence of new hormonal deficiency. The overall DC was achieved in 20 (57.1%). The NFPAs achieved GTR in 6 (54.5%) and STR in 2 (18.2%) patients, while FPAs achieved DC in 25 (58.3%) patients. Pre-existing hormonal deficiency recovered in at least one hormonal axis in 10 (55.5%) patients, among which the gonadal axis was the most 5 (14.3%) recovered one. New hormonal deficiencies post-ETSs were documented in 12 (34.3%) patients in which prolonged DI was the most frequent 11 (31.4%). Imaging at six-month post-ETSs revealed absence of PPBS in 9 (25.7%) patients [Table 2, and 3].

Variables associated with ETSs outcomes

Association of post-ETSs outcome with tumor characteristics and surgeon experience were evaluated. The DC in FPAs were significantly associated with smaller tumor size (P = 0.029). While, DC in patients with NFPAs was significantly associated with less (moderate and low) experienced surgeons (P = 0.022) [Table 4].

At six-month post-ETSs, there was significant association between recovery of at least one pre-existing pituitary hormonal deficiency with smaller tumor size (P = 0.027), furthermore persistence of new hormonal deficiency in at least one pituitary axis was significantly associated with larger adenomas (macroadenoma/ giant adenoma), higher Knosp grades, and low-experienced surgeons (P = 0.028, 0.014, and 0.002 respectively) [Table 5].

Because the earlier results showed the ADH as predominantly involved hormone deficiency, we further evaluated the association of early water dysregulation and prolonged DI with the same variables. Both early water dysregulation and Prolonged DI was significantly associated with larger tumor sizes (P = 0.005, and 0.031 respectively). Additionally, prolonged DI significantly associated with higher Knosp grades, high- and low-experienced surgeon and the absence of PPBS post-ETSs (P = 0.012, 0.005, and 0.001 respectively).

The occurrence of early post-ETSs water dysregulation was significantly associated with prolonged hospital stay (P = 0.035), and all patients who required readmission were experienced water dysregulation despite it was statistically insignificant (P = 0.259) [Table 6].

This is the first prospective study addressing ETSs endocrine outcome in Iraq. Erbil city is one of the major drainage areas for ETSs.

Disease control

The total (FPA and NFPA) achieved DC was 20 (57.1%), that was lower than Ismail et al (2016) study which reported DC to be as high as (67%) [9]. Similarly, Kabil et al (2005) study reported DC by (88%) [14]. In our study, DC among patients with FPAs was 14 (58.4%), which was lower than Chone et al. (2014) [15]. study that reported (87%) hormonal control among FPAs. While we reported a higher DC rate among NFPAs 6 (54.5%) than Møller et al. (2011) study (39%) [16], however this rate remains lower than the GTR rates of (93%) and (83%) reported by Kabil et al. (2005) and Little AS et al. (2020), respectively [14, 17].

Prior studies have shown that tumor characteristics and surgeon experience are significant predictors of DC and may aid to explain the variabilities in outcomes [4]. In our study tumor size was insignificantly associated with DC among NFPAs, while it significantly influenced treatment success in FPAs (P = 0.029) as all patients with microadenomas achieved DC, whereas only 10/18 (54.2%) patients with macroadenomas attained DC. None of the NFPAs was microadenoma, this can explain our findings and also align with previous studies, suggesting that microadenomas are more accessible for resection, whereas macroadenomas may exhibit more aggressive behavior, potentially invading surrounding tissues and complicating surgery and the postoperative period [18–20]. However, the significant association between less experienced surgeons and a higher GTR rate (P = 0.022) is noteworthy. Unexpectedly, both less experienced and moderately experienced surgeons demonstrated a greater success rate in achieving complete tumor resection. This might be explained by the small sample size, complex cases managed by experienced surgeons, and the extra time less experienced surgeons dedicate to their techniques. Additionally, more experienced surgeons may opt for less aggressive techniques to minimize tissue damage and reduce the risk of new hormonal deficiencies, especially considering our study's finding of higher rate of new hormonal deficiencies among less experienced surgeons (mentioned below).

Additionally, the tumor characteristics of our study population were largely consistent with those reported in the aforementioned studies [9, 14–17], despite that we observed lower DC compared to these studies. This decline may be attributed to the low experience of our surgical teams as the surgery has recently gained popularity in our locality. This finding warrants further investigation of the contributing factors and might necessitate modifications in the local surgical approach.

Hormonal Recovery

About 10/18 (55.5%) patients had recovered at least one hormone post-ETSs. The gonadal axis was the most frequently recovered hormone 5/11 (45.5%). This recovery rate was higher than that reported by Mavromati et al. (2023), who reported a recovery rate of (46%) in one or more pituitary hormones and gonadal axis recovery (35.7%) [21], and higher than Hantelius et al. (2024) report (17.6%) [22]. Our finding suggests a favorable outcome particularly in terms of gonadal hormone recovery following ETSs given the complexities and high cost associated with the management of central hypogonadism.

The significant association of recovery of deficient pituitary hormones with smaller tumor size (P = 0.027) aligns with Alexopoulou et al. (2021) study which supports early surgical intervention in patients with pituitary macroadenomas and hormonal deficiencies, independent of visual disturbances [23].

New hormonal deficiencies

A considerable proportion of patients developed new hormonal deficiency 12 (34.3%) in at least one axis post-ETS, which falls between the rates reported by Molteni et al. (2023) at (53.3%) and Mavromati et al. (2023) at (9.6%) [24, 21]. Our high rate of new hormonal deficiency contributed mainly to the occurrence of DI. Prolonged DI found in 11 (31.4%) patients and occurred with or without other pituitary hormonal deficiencies. The incidence of prolonged DI post-ETSs was reported as low as (1.5%) by Ismail et al. (2016) and as high as (52.7%) by Fathallah et al. (2015) [9, 25]. Comparing with these studies, the current study had higher rate of DI. This finding necessitates proactive evaluation and management.

In our study, macroadenomas, giant pituitary adenomas, and apoplexy, constituted the majority of pituitary lesions 29 (82.9%) patients. While cavernous sinus invasion was identified in 26 (80%) patients. These characteristics may elucidate the increased incidence of new hormonal deficiencies, including DI. These findings align with findings from Nemergut et al. (2005) and Nayak et al. (2018) who noted that larger tumor sizes serve as predictor for the development of new hormonal deficiency including DI [26, 27]. Furthermore, Araujo-Castro et al. (2018) reported that Knosp grades 3 and 4 are associated with a greater likelihood of complications following pituitary adenoma surgery [28]. Additionally, since the incidence of new hormonal deficiency (including DI) is associated with the surgeons’ experience, this relatively high incidence should probably be reduced by improving the surgical skills of ETSs.

A significant association between prolonged DI and absence of PPBS (P = 0.001) supported with findings by Colombo et al (1987) [29]. Absence of PPBS can be utilized as a diagnostic marker considering the complexity of the biochemical tests.

The significant association of early water dysregulation with prolonged hospital stays (P = 0.035), along with the observation of early water dysregulation in all readmitted patients, points toward the importance of preventing water dysregulation in reducing patient morbidity and health care cost, these findings are consistent with Brooks et al. (2023) results [30].

Limitation

Sample size was small due to missed follow up of many patients, this can affect the generalizability of our results. For GH assessment, we used clonidine stimulation test which can overestimate GH deficiency. Because of the unavailability of osmometer, we depended on calculated (rather than measured) serum and urine osmolalities which can give inaccurate results.

In Erbil, Iraq, post-ETSs overall DC was lower than internationally reported DC. Additionally, although a considerable proportion of patients experienced pituitary hormone recovery, there were higher rates of new hormonal deficiencies (particularly ADH) post-ETSs. The DC rates, and changes in pituitary hormones post-ETSs were significantly associated with tumor characteristics and surgeon experience, highlighting the importance of improving surgical skills in preventing complications. Early water dysregulation post-ETSs significantly associated with longer hospital stay. However, the relationship between early water dysregulation and higher readmission rates was statistically insignificant, despite the fact that all patients who were readmitted exhibited water dysregulation. This condition might contribute to greater patient morbidity and increased healthcare costs.

ACTH: Adrenocorticotropic hormone

ADH: Antidiuretic hormone

DC: Disease control

DI: Diabetes insipidus

ETSs: Endoscopic transsphenoidal surgery

FPA: Functioning pituitary adenoma

FSH: Follicular stimulating hormone

FT4: Free thyroxine

GH: Growth hormone

GTR: Gross total resection

IGF-1: Insulin-like growth factor-1

LH: Luteinizing hormone

MRI: Magnetic resonance imaging

NFPA: Non-functioning pituitary adenoma

ODST: Overnight dexamethasone suppression test

OGTT: Oral glucose tolerance test

PPBS: Posterior pituitary bright spot

PR: Partial resection

SIADH: Syndrome of inappropriate antidiuretic hormone

STR: Subtotal resection

Funding

We declare that this study is not funded by any external sources.

Author Contribution

All authors have reviewed the final version to be published and agreed to be accountable for all aspects of thework.Concept and design: A.N., Y. A.Acquisition, analysis, or interpretation of data: A.N., Y. A.Drafting of the manuscript: A.N., Y. A.Critical review of the manuscript for important intellectual content: A.N., Y. A.Supervision: Y.A.

Acknowledgement

I would like to express my gratitude to my colleagues Breshan E. (C.A.B. M.S. in Internal Medicine) and Narmin E. (MSc in Pharmacy) for their valuable assistance with this manuscript.

Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

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Table 1: Pre-operative demographic characteristics of study population

Variables	N (%)
Gender
Male	15 (42.9)
Female	20 (57.1)
Age (years)
≤15	1 (2.9)
16-30	6 (17.1)
31-45	15 (42.9)
>45	13 (37.1)
Type of tumor
NFPAs	11 (31.4)
FPAs	24 (68.6)
Acromegaly	13 (37.1)
Cushing’s disease	7 (20)
Prolactinoma	4 (11.4)
Tumor size
Microadenoma	6 (17.1)
Macroadenoma	24 (68.6)
Giant adenoma	2 (5.7)
Pituitary Apoplexy	3 (8.6)
Knosp classification
Grade 0	7 (20)
Grade 1	0 (0)
Grade 2	12 (34.3)
Grade 3	10 (28.6)
Grade 4	6 (17.1)
Pre-existing hormonal deficiency
Yes	18 (51.4)
No	17 (48.6)
ETSs per surgeon experience
High	15 (42.9)
Moderate	14 (40)
Low	6 (17.1)

ETSs: endoscopic transsphenoidal surgery; FPAs: functional pituitary adenomas; NFPAs: non-functional pituitary adenomas.

Table 2: Early and late endocrine outcome post endoscopic transsphenoidal surgery

Variable	N (%)
Early outcome
Hospital stay (days) (N=35)
1 to 3	22 (62.9)
4 to 6	6 (17.1)
7 or more	7 (20)
Re-admission rate (N=35)
Yes	3 (8.9)
No	32 (91.4)
Water dysregulation (N=35)
Absent	14 (40)
Early DI	14 (40)
Triphasic response	5 (14.3)
Isolated SIADH	2 (5.7)
Early ACTH deficiency (N=28)∞
Occurred	4 (11.4)
Not occurred	24 (85.7)
Late outcome
NFPAs disease control (N=11)
GTR	6 (54.5)
STR	2 (18.2)
PR	3 (27.3)
FPAs disease control (N= 24)
Controlled acromegaly	7 (53.84)*
Controlled Cushing’s disease	5 (71.42)**
Controlled prolactinoma	2 (50)***
Total uncontrolled FPAs	10 (41.6)
Recovery of pre-existing hormonal deficiency (N= 18)¶
No hormonal recovery	8 (44.4)
One or more axis recovery	10 (55.6)
New hormonal deficiency (N= 35)
Yes	12 (34.29)
No	23 (65.71)
PPBS at 6^th month
Observed	26 (74.3)
Absent	9 (25.7)

∞ Cushing’s disease was excluded; * from total acromegaly patients; ** from total Cushing’s disease patients; *** from total prolactinoma patients; ¶ seventeen patients had no pre-existing hormonal deficiency; ACTH: adrenocorticotropic hormone; DI: diabetes insipidus; ETSs: endoscopic transsphenoidal surgery; FPAs: functional pituitary adenomas; GTR: gross total resection; NFPAs: non-functional pituitary adenomas; PPBS: posterior pituitary bright spot; PR: partial resection; SIADH: syndrome of inappropriate antidiuretic hormone; STR: subtotal resection.

Table 3: Changes in pituitary hormones pre- and six-month post endoscopic transsphenoidal surgery

-	No change (Normal/ Normal)¶ N (%)	No change (Impaired/ Impaired)¶ N (%)	Recovered N (%)	Impaired N (%)
TSH (N=35)	20 (57.1)	7 (20)	3 (8.6)	5 (14.3)
ACTH* (N=28)	19 (67.9)	5 (17.9)	2 (7.1)	2 (7.1)
Prolactin** (N=31)	26 (83.9)	4 (11.4)	0 (0)	1 (3.2)
GH*** (N=22)	17 (77.3)	3 (8.6)	0 (0)	2 (9.1)
FSH/LH (N=35)	23 (65.7)	6 (17.1)	5 (14.3)	1 (2.9)
ADH (N=35)	24 (68.6)	0 (0)	0 (0)	11 (31.4)

¶ (pre ETSs/ post ETSs); * Cushing’s disease was excluded; ** Prolactinomas were excluded; *** Acromegaly was excluded

Table 4: Association of disease control post endoscopic transsphenoidal surgery with tumor characteristics and surgeon experience

Characteristics	NFPAs DC status (N=11)			FPAs DC status (N=24)
Characteristics	Controlled (N=6)	Uncontrolled (N=5)	P-value	Controlled (N=14)	Uncontrolled (N=10)	P-value
Tumor size (N)
Microadenoma	0	0	0.130	6	0	0.029*
Macroadenoma	3	4		7	10
Giant adenoma	0	1		1	0
Pituitary Apoplexy	3	0		0	0
Knosp classification (N)
Grade 0	0	0	0.535	6	1	0.086
Grade 2	3	1		5	3
Grade 3	2	2		1	5
Grade 4	1	2		2	1
ETSs per surgeon experience (N)
High	1	5	0.022*	5	4	0.247
Moderate	3	0		8	3
Low	2	0		1	3

* Significant P = at <0.05; DC: disease control; ETSs: endoscopic transsphenoidal surgery; FPAs: functional pituitary adenomas; NFPAs: non-functional pituitary adenomas.

Table 5: Association of pituitary hormonal changes post endoscopic transsphenoidal surgery with tumor characteristics and surgeon experience

Characteristics	Recovery of pre-existing pituitary hormone deficiency (N=18)			New pituitary hormonal deficiency (N=35)
Characteristics	No Recovery (N=8)	One or more axis recovery (N=10)	P-value	No deficiency (N=23)	One or more axis deficiencies (N=12)	P-value
Tumor size (N)
Microadenoma	0	2	0.027*	6	0	0.028*
Macroadenoma	3	8		13	7
Giant adenoma	2	0		1	5
Pituitary Apoplexy	3	0		3	0
Knosp classification (N)
Grade 0	1	2	0.159	7	0	0.014*
Grade 2	2	6		9	3
Grade 3	2	2		6	4
Grade 4	3	0		1	5
ETSs per surgeon experience (N)
High	3	5	0.869	7	8	0.002*
Moderate	3	3		14	0
Low	2	2		2	4

* Significant P = at <0.05; ETSs: endoscopic transsphenoidal surgery.

Table 6: Association of antidiuretic hormone disturbance post endoscopic transsphenoidal surgery with tumor characteristics and surgeon experience

Characteristics	Early water dysregulation			Prolonged DI
Characteristics	Occurred (N=21)	Not occurred (N=14)	P-value	Yes (N=11)	No (N=24)	p-value
Tumor size (N)
Microadenoma	1	5	0.005*	0	6	0.031*
Macroadenoma	18	6		9	15
Giant adenoma	2	0		2	0
Pituitary Apoplexy	0	3		0	3
Knosp classification (N)
Grade 0	2	5	0.197	0	7	0.012*
Grade 2	7	5		3	9
Grade 3	8	2		3	7
Grade 4	4	2		5	1
ETSs per surgeon experience (N)
High	10	5	0.187	8	7	0.005*
Moderate	6	8		0	14
Low	5	1		3	3
PPBS (N)
Observed	NA	NA		2	24	0.001*
Absent	NA	NA		9	0
Hospital stay (days)
1-3	12	10	0.035*	NA	NA	-
4-6	2	4		NA	NA
≥7	7	0		NA	NA
Readmission rate (N)
Yes	3	0	0.259	NA	NA	-
No	18	14		NA	NA	-

* Significant P = at <0.05; ETSs: endoscopic transsphenoidal surgery; NA: not applicable; PPBS: posterior pituitary bright spot at six-month.

No competing interests reported.

Endocrine Outcomes Following Endoscopic Transsphenoidal Pituitary Surgery in Erbil, Iraq

Status:

Version 1

Abstract

Objective

Methods

Results

Conclusion

Introduction

Materials and Methods

Study design

Inclusion criteria

Exclusion criteria

Surgical Team

Endocrine and neuroradiology assessment

Post-ETSs monitoring for DC

Post-ETSs monitoring for hormonal deficiency

Statistical analysis

Results

Discussion

Disease control

Hormonal Recovery

New hormonal deficiencies

Limitation

Conclusion

Abbreviations

Declarations

Funding

Author Contribution

Acknowledgement

Data Availability

References

Tables

Additional Declarations

Status:

Version 1