Study of management strategies in ACTH secreting pituitary microadenoma of Cushing disease

Background: Pituitary Microadenomas can be defined as small lesions less than 1 cm in the pituitary and detected as incidentalomas. Partial development or late development around puberty leads to maldevelopment of secondary sexual characteristics due to pituitary adenomas. Clinically this may manifest as secondary amenorrhoea and may lead to hyperprolactinaemia, galactorrhoea and Amenorrhoea. ACTH secreting micro adenomas of the Pituitary Gland is a clinical entity where the role of surgery is contemplated. This study attempted to explore the management options and strategies for pituitary microadenomas. The aim of the study: To highlight the characteristics of Cushing’s disease and discuss the management strategies including trans-sphenoidal surgery to treat ACTH secreting pituitary microadenomas. Materials and methods: This was a non-randomised prospective observational study involving all adrenal tumors from 2007-2017 in Madras Medical College, Chennai. Two adrenocortical adenomas M.S. Senthil Kumar, Rajan Ganesan, A. Nithyanandham, V. Kannan, T. Suresh Babu, K. Prabhakaran. Study of management strategies in ACTH secreting pituitary microadenoma of Cushing’s disease. IAIM, 2019; 6(3): 253-258. Page 254 with virilising features were ruled out and 8 ACTH secreting Cushing's disease with microadenomas were identified. 3 Patients with ACTH secreting microadenomas of Cushing's disease underwent surgery whereas 3 underwent medical treatment based on which this paper attempted to discuss management strategies for Cushings disease. Results: ACTH levels were measurable with an average of 136.71pg/ml (normal 7.2-63.3 pg/ml) Corticotrophin releasing hormone test was planned to evaluate an exaggerated response of serum cortisol consistent with pituitary disease. It was not carried out and inferior petrosal sampling also was not done. Biochemical evaluation confirmed pituitary dependent Cushing’s disease. MRI revealed a prominent circumscribed lesion suggestive of a Pituitary Micro Adenoma in All 6 Cases. Conclusion: Pituitary micro adenomas are operable and in Cushing’s disease offer an effective cure. The outcome is good with minimal complications, but surgeons must have a thorough knowledge of the surrounding anatomy and potential complications.

A patient with Cushing disease lateralizing a pituitary adenoma by inferior petrosal sinus sampling using desmopressin: a case report

A 14-year-old girl was referred for evaluation of the etiology of Cushing syndrome. During the previous 2 years, she had experienced weight gain, secondary amenorrhea, growth retardation, and back pain. Random serum cortisol level, 24-hour urinary free cortisol excretion, and overnight and low-dose dexamethasone suppression tests suggested Cushing syndrome. Midnight adrenocorticotropic hormone (ACTH) level and high-dose dexamethasone suppression test confirmed Cushing disease. Pituitary magnetic resonance imaging was suspicious for microadenoma. To eliminate ectopic ACTH syndrome, and lateralize the pituitary tumor, inferior petrosal sinus sampling (IPSS) was performed by desmopressin use to stimulate ACTH. Finally, the patient was diagnosed with Cushing disease due to ACTH-secreting pituitary microadenoma, lateralized to the left side; subsequently underwent transsphenoidal surgery. Here we report a case of a 14-year-old girl diagnosed with Cushing disease with a pituitary tumor lateralized by IPSS using desmopressin, which is very rare in pediatric Cushing disease.

Using Growth Hormone Levels to Detect Macroadenoma in Patients with Acromegaly

BACKGROUND: The aim of this study was to assess the clinical differences between acromegalic patients with microadenoma and patients with macroadenoma, and to evaluate the predictive value of growth hormone (GH) levels for early detection of macroadenoma. METHODS: We performed a retrospective analysis of 215 patients diagnosed with a GH-secreting pituitary adenoma. The patients were divided into two groups: the microadenoma group and the macroadenoma group, and the clinical parameters were compared between these two groups. The most sensitive and specific GH values for predicting macroadenoma were selected using receiver operating characteristic (ROC) curves. RESULTS: Compared with the microadenoma group, the macroadenoma group had a significantly younger age, higher body mass index, higher prevalence of hyperprolactinemia and hypogonadism, and a lower proportion of positive suppression to octreotide. However, there were no significant differences in the gender or in the prevalence of diabetes between the two groups. The tumor diameter was positively correlated with all GH values during the oral glucose tolerance test (OGTT). All GH values were significantly higher in the macroadenoma group than the microadenoma group. Cut-off values for GH levels at 0, 30, 60, 90, and 120 minutes for optimal discrimination between macroadenoma and microadenoma were 5.6, 5.7, 6.3, 6.0, and 5.8 ng/mL, respectively. ROC curve analysis revealed that the GH value at 30 minutes had the highest area under the curve. CONCLUSION: The GH level of 5.7 ng/mL or higher at 30 minutes during OGTT could provide sufficient information to detect macroadenoma at the time of diagnosis.

Clinical characteristics and diagnostic analysis of thyrotropinoma / 中华内分泌代谢杂志

Objective To analyze clinical charaCteristics and diagnostic experience on thyrotropinoma (TSHoma).Methods Clinical characteristics,laboratory findings,diagnostic experience,and surgical outcome were summarized from 16 cases of TSHoma in our hospital from January 2006 to September 2011.Results ( 1 )Among 16 cases ( 9 male,7 female ) aged ( 51.63 ± 13.23 ) years,14 ( 87.5 ％ ) cases presented with hyperthyroidism and 2 were diagnosed by physical examination. None of them had exophthalmos, acropachy, or pre-tibial myxedema.( 2 ) Serum FT4 and FT3 levels were all above normal range with serum TSH ( 4.37 ± 2.77 ) μIU/ml.There were 25％ (4/16) cases with positive serum thyroglobulin antibody and/or thyroid peroxidase antibody,none with positive TSH receptor antibody.TRH stimulating test was performed in 9 cases,3 were with positive response ( peak TSH level increased by 5.45-9.20 μIU/ml compared with baseline),and 6 without response (peak TSH level increased by -0.01-3.15 μIU/ml compared with baseline).TSH was suppressed to 27.15％ (5.19％-99.15 ％ ) of the baseline in 11 cases in which somatostatin suppression test was carried out.Prolactin and insulin-like growth factor-Ⅰ levels were increased in 2 cases.MRI performed in 15 patients showed 10 cases of microadenomas and 5 cases of pituitary adenoma.A mass in nasal cavity was found in one case,where no mass was found in the pituitary.( 3 )Surgery was made in 11 cases ( 9 patients underwent transsphenoidal operation,one craniotomy,and one underwent operation via endoscopic nasal septum ). All patients (11/11) were proved to yield pituitary adenoma pathologically.Conclusion Thyrotropinoma should be considered in hyperthyroidism with unsuppressed TSH level,and dynamic tests facilitated early diagnosis.Ectopic thyrotropinoma shoull be considered when normal pituitary morphology was shown by MRI.

Resonancia magnética en adenomas de hipófisis / Magnetic resonance imaging in pituitary adenomas

Objetivo: Relacionar las imágenes de los adenomas obtenidos mediante RM para su mejor caracterización mediante un protocolo de alta resolución. Material y Métodos: Se analizaron retrospectivamente 86 RM de la región selar realizadas en el Hospital Obrero N°1, y se las relacionó con el tipo de realce post contraste paramagnético y signos de compresión. Se estudiaron 72 mujeres y 14 hombres, con un promedio de 43 años. Las exploraciones se realizaron utilizando un Magneto Signa 1,5 T, con cortes sagitales y coronales ponderados en T1 sin y con contraste paramagnético. Resultados: • El 67,5% (58 pacientes) presentó adenoma hipofisiario. De estos el 51.1% fueron tipo microadenoma y el 48.3% macroadenoma. • El 53,3% de los microadenomas y el 14,3% de los macroadenomas presentaban hiperprolactinemia. • El 100% de los macroadenomas presentaron realce heterogéneo tras la administración del medio de contraste. Los microadenomas presentaron realce homogéneo en el 76,6%. • El 85,7% de los macroadenomas y el 16,7% de los microadenomas presentaron obliteración de la cisterna supraselar. • El 85,7% de los macroadenomas y en el 10% de los microadenomas, produjeron desplazamiento del quiasma óptico. • El 64,3% de los macroadenomas y en el 20,7% de los microadenomas, invadieron el seno cavernoso y desviaron el tallo hipofisiario. Conclusión: La RM es el método imagenológico de elección para el estudio de la hipófisis gracias a su caracterización anatómica y funcional, especialmente cuando se utiliza gadolinio.

Objective: To relate the images of adenomas obtained by MRI for further characterízation using a high-resolution protocol Material and Methods: We analyzed 86 MRI retrospectivamen the sellar region in the Hospital Obrero No. 1 and are related to the type of contrast enhancement after paramagnetic and signs of compression. We studied 72 women and 14 men with an average of 43 years gave. The scans were performed using Magneto do a 1.5 T Signa, with cut-weighted sagittal and coronal T1 with and without paramagnetic contrast. Results: • 67.5% (58 patients) had pituitary adenoma. Of these the kind microadenomas were 51.1% and 48.3% macroadenoma. • 53.3% of microadenomas and 14.3% of macroadenomas had hyperprolactinemia. • 100% of the macroadenomas showed heterogeneous enhancement after administration of contrast medium. The microadenomas showed homogeneous enhancement in 76.6%. • The 85.7% of macroadenomas and 16.7% of microadenomas showed obliteration of the tank supraselar. • The 85.7% of macroadenomas and10% of microadenomas, produced displacement of optic chiasm. • 64.3% of macroadenomas and 20.7% of microadenomas, invaded the cavernous sinus and diverted the pituitary stalk. Conclusión: MRI is the imaging method of choicefor the study of the pituitary due to its characterisation in anatomy and function especially when using gadolinium.

Endonasal Endoscopic Transsphenoidal Pituitary Surgery for Pituitary Adenoma: A retrospective Analysis Of Surgical Outcome

The purpose of this retrospective joint rhino-neurosurgical study from January 1998 until September 2009 is to document the demographic data, clinical presentations, radiological findings, approaches and incidence of residual tumour. Forty-seven patients with pituitary adenoma underwent trans-sphenoidal hypophysectomy of which 25 patients with complete medical and radiological data were included in the study. The medical and radiological data were analyzed. There were 12 males and 13 females with age ranging from 17 to 76 years old (mean 49.2). Fourteen of the patients were Chinese, eight Malays and three Indians. Twelve of the patients had functioning tumour of which five each presented with acromegaly and Cushing disease respectively and two with amenorrhoea. The rest of 13 patients had non functioning tumour presenting with visual disturbances. Sixteen of the patients had pituitary macroadenomas and the rest 9 microadenomas. Eighteen patients had undergone transcollumellar trans-sphenoidal hypophysectomy and the rest 7 patients had undergone transnasal transsphenoidal hypophysectomy. About 68.8% of pituitary macroadenomas had residual tumour, compared to only 22.2% of patient with pituitary microadenomas. Radiologically, about 45.5% of residual macroadenoma had suprasellar extension and the majority had spread to suprasellar cistern and carvenous sinus (54.5%). About 16.6% of patients had undergone post operative radiotherapy. In conclusion, this study showed that patient with pituitary macroadenomas had higher incidence of residual tumour compared to pituitary microadenomas

Diagnosis and treatment of pediatric and hebetic adrenocorticotropic hormone secreting pituitary microadenoma / 上海交通大学学报（医学版）

Objective To investigate the methods of diagnosis and treatment of pediatric and hebetic adrenocorticotropic hormone ( ACTH) secreting pituitary microadenoma. Methods The data of 10 patients with ACTH secreting pituitary microadenoma were retrospectively analysed. ACTH secreting pituitary microadenoma was diagnosed by clinical manifestations, biochemical and imaging findings, and 5 patients underwent bilateral inferior petrosal sinus sampling ( BIPSS). Transsphenoidal surgery was performed on all the patients under microscope, and the tumor specimens were detected by immunohistochemistry. Results Immunohistochemical examination revealed that ACTH was positive in 8 cases and negative in 2 cases. Patients were followed up for 12 to 63 months, 7 cases (70%) were cured, one (10%) achieved remission, and the other two (20%) experienced recurrence. Conclusion BIPSS is helpful in the diagnosis and localization of pediatric and hebetic ACTH pituitary microadenoma, and transsphenoidal surgery is the optimal choice of treatment.

A TSH-secreting pituitary microadenoma diagnosed with inferior petrosal sinus sampling: Case report / 대한내과학회지

Thyroid stimulating hormone (TSH)-secreting pituitary adenomas are rare tumors of the pituitary gland and represent 1~2% of all pituitary adenomas. A TSH-secreting pituitary adenoma shows as a normal or elevated thyrotropin level in a hyperthyroid patient. We present a 32-year-old woman who was diagnosed with a TSH-secreting pituitary microadenoma. She had a high free T4, with a normal TSH and alpha-subunit. Bilateral inferior petrosal sinus sampling (IPSS) was done to confirm the alpha-subunit secreting adenoma, and the concentration of the alpha-subunit was high on the tumor side. The pituitary microadenoma was removed, and her TSH and free T4 levels decreased to normal. IPSS may help give an accurate diagnosis in the patient with a normal alpha-subunit.

Adenoma microquístico pancreático: reporte de caso / Pancreatic microcystic adenoma: case report

Se revisan las manifestaciones clínicas y diagnósticas del adenoma microquístico pancreático. Para ello, se aporta nuestra experiencia con un caso: paciente masculino, 54 años de edad, diabético tipo II controlado con sulfonilureas durante 4 años, hipertenso controlado con bloqueadores de los canales de calcio durante 2 años. La manifestación clínica más significativa fue dolor en epigastrio irradiado en hemicinturón, de tres días de evolución. Hemograma y bioquímica sanguínea dentro de límites normales; eco abdominal reporta presencia de tumor de 2cm en cabeza del páncreas, por lo que se solicita TAC a doble contraste, la que confirma la presencia de tumoración, con zonas de calcificación. Se realiza intervención quirúrgica para la excéresis y estudio histopatológico, luego de lo cual el paciente evoluciona favorablemente.

Clinical features and diagnostic criteria of the pancreatic microcyst adenoma are checked in this study. For that, we contribute with our experience through this case: male patient, 54 years old, type II diabetic controlled with sulfonylureas for 4 years, hypertensive controlled with calcium channels blockers for 2 years. The most significant clinical feature was epigastralgia with a one side girdling radiation, three days long. Hemogram and blood chemistry within normal limits; abdominal echography reports the presence of a 2cm tumor in the head of the pancreas, which is why a double contrast CAT was requested. This scan confirmed the presence of the tumor with calcification zones. Surgery was performed for exeresis and histopathological study. Afterwards, the patient makes satisfactory progress.

Diagnostic Value of Magnetic Resonance Imaging Examination for Pituitary Hypertension Complicated with Pituitary Microadenoma / 广州中医药大学学报

Objective To investigate the relationship between the secondary hypertension and pituitary microadenoma,and to explore the diagnostic value of magnetic resonance imaging(MRI) examination for pituitary microadenoma.Methods We analyzed the clinical information,laboratory examination results and imaging data in 21 hypertension patients complicated with pituitary microadenoma.Results The manifestations of the 21 patients were as follows:(1) The onset of hypertension was in young age,complicated with headache;(2) The results of 24-hour ambulatory blood pressure monitor(24h ABPM) showed the disappearance of circadian rhythm of blood pressure,and obvious increase of systolic/diastolic blood pressure;(3) The antihypertensive effect of antihypertensive drugs was not satisfactory;(4) Of adenohypophyseal hormones,adrenocorticotrophic hormone(ACTH) level in most patients and prolactin(PRL) level in a few patients were higher than the normal level,and the other hormones levels were normal;(5) The results of MRI examination presented adrenal cortical hyperplasia,adrenal adenoma and chromaffin tumor in some patients.(6) The results of MRI examination showed pituitary microadenoma in all of the patients.Conclusion For those middle-aged and young hypertension patients on whom antihypertensive effect of drugs is poor,MRI examination for adrenal gland and pituitary gland should be taken as the routine examination.MRI examination is the optimal imaging method for pituitary microadenoma,and supply evidence for the syndrome differentiation and treatment of pituitary microadenoma.

The Results of Transsphenoidal Microsurgery for Pituitary Microadenama in Cushing's Disease / 대한내과학회지

BACKGROUND: Cushing's disease is a hypercortisolic state attributable to hypersecretion of ACTH at pituitary gland Most of these diseases are due to pituitary microadenoma. Selective removal of adenoma by transsphenoidal microsurgery is the treatment of choice for Cushing's disease. We evaluated 25 cases to analyze results of transsphenoidal microsurgery and to identify prognostic factors that may predict successful outcome. METHODS: From 1989 to 1995, 25 patients were diagnosed as having Cushing's disease in Seoul National University Hospital. They were underwent pituitary microsurgery and confirmed to have pituitary microadenoma radiologically and pathologically. About these patients. retrospective evaluation was done. RESULTS: The patients consist of 21 females and 4 males and the age was ranged from 23 to 49 years. 19 patients (76%) were judged as immediate remission. The preoperative clinical, hormonal, and radiological characteristics of the remission and failure groups were similiar The patients who were immediate remission were followed from 3 months to 72 months. 3 patients had recurrences(15.8%) at 4, 8, 49 months after operation. The pre and postoperative clinical, hormonal, and radiological characteristics of the long-term remission and recurrence groups were similiar. We could not find any predictable factors of surgical outcome. CONCLUSION: The first line trearment of Cushing's disease is transsphenoidal microsurgery. However considering relative late and high rate of recurrence of Cushing's disease following curative surgery, careful longterm follow up is mandatory.

A Case of True Precocious Puberty Associated with Pituitary Microadenoma Treated with LHRH Agonist / 대한내분비학회지

Recently Brain CT and MRI have greatly contributed to the discovery of intracranial tumors including cysts which cause precocious puberty. Among many precocious pubetry patients that had previously been diagnosed as idopathic, a number of cases turn out the true precocious puberty caused by intracranial lesion.Authors experienced a case of true precocious puberty in a seven year old female whose vaginal bleeding appeared at age of five and she also had breast enlargement on admission. Pituitary microadenoma was found on her brain MRI and the microadenoma turned to be nonfunctional on hormonal tests.Following three does of decapety1-CR(LHRH Agonist), the vaginal bleeding was ceased and the deceleration of breast enlargement was noted. Her growth velocity was also affected but the further observation for final height would be warranted.

Clinical Analysis of Sellar Tumors Treated via Transsphenoidal Route

Between January 1990 and August 1992 sixteen patients with sellar tumors underwent 16 transsphenoidal approaches at Kang-Nam Sacred Heart Hospital. Pathological diagnosis include 14 pituitary adenomas, of which six belonged to microadenomas and the remaining eight cases were classified as macroadenomas. Other pathologies were one craniopharyngioma and one sphenoid mucocele. Thirteen patients underwent TSA as the primary procedures and the remaining three patients were subjected to TSA as the secondary procedures to the primary treanscranial approaches. Of the 13 primary TSAs excellent or good results were achieved in 11 patients and the remaining two patients were subjected to the secondary transcranial approaches to achieve good results. Six patients with microadenomas achieved gross total or subtotal removal of their tumors in all cases(100%) however, satisfactory removal was achieved only in six macroadenoma cases(75%). There was neither surgical mortality nor major morbidity. Transient diabetes insipidus complicated in 6 patients(37.5%) and CSF rhinorrhea complicated in three cases*18.8%), which needed spinal drainage for three to ten days. Meningitis was complicated in one patient with CSF rhinorrhea(6.2%). This preliminary study agrees with that TSA is a safe and effective procedure even in macroadenoma cases.

Thyrotropin-secreting pituitary microadenoma

We present a 45-yr-old male with clinical signs and symptoms of mild hyperthyroidism, high serum levels of T3, T4, and FT4 as well as serum TSH concentration. The elevated alpha-subunit level and alpha-subunit/TSH molar ratio were also observed. These findings indicated the presence of hyperthyroidism due to inappropriate secretion of TSH, whose neoplastic origin was documented by nuclear magnetic resonance scan showing a 0. 6 cm pituitary adenoma. Selective pituitary adenomectomy was completely successful; alpha-subunit, TSH, T3, T 4, and FT4 normalized, and euthyroidism was restored. Light microscopic immunohistochemistry showed that the adenoma was composed of TSH-secreting cells

Cushing's Disease: Clinical Analysis and Surgical Outcome in 16 Cases

From March, 1984 to August, 1991, 16 patient were diagnosed as Cushing's disease and 14 of them were treated by transsphenoidal microsurgical procedure. Preoperrative endocrinological evaluation included plasma level of ACTH, serum cortisol concentration, urinary free cortisol and 17-hydroxycorticosteroid, dexamethasone suppression test and bilateral sampling of the inferior petrosal sinuses(IPS). The sensitivity of the last method was 88% for Cushing's disease but the expected laterality with the test was not always consistent with the surgical results. High resolution computed tomography(CT) and high field magnetic resonance imaging(MRI) were done as imaging devices. We cannot tell MRI is superior to CT is diagnosing microadenomas. All operations were performed through transsphenoidal approach. A selective microadenomectomy was done in 8 patients and all of them showed remission. A partial adenomectomy was done in 4 cases. Hypophysectomy was done in 2 cases, one of which was a failed case after the first trial and the other was one with no apparent tumor tissue in 7 successive frozen biopsies during operation. Overall surgical remission rate was 86.

Cushing′s disease: a comparison between pituitary macroadenoma and microadenoma / 中华内分泌代谢杂志

Objective To compare the difference of clinical characteristics between patients with pituitary corticotroph macroadenoma and microadenoma. Methods From 1985 to 1998, 76 inpatients with Cushing′s disease, 12 cases of macroadenoma and 64 cases of microadenoma were reviewed. The clinical manifestations, the course before diagnosis, blood routine, biochemical and endocrinic examinations were retrospectively analyzed. Results Defect of vision field and galactorrhea were more frequent and the duration of disease before diagnosis were shorter in macroadenomas than those in microadenomas. Lymphopenia, hypokalaemia, lower creatine kinase level and hyperphosphoroemia were also more pronounced in macroadenomas. In macroadenomas, the plasma ACTH and cortisol (F) concentrations at 0:00 were obviously higher than those in microadenomas, but plasma ACTH and F at 8:00 and 24h urinary free cortisol were similar in these two groups. The relative nyctohemeral variation of ACTH was less in macroadenomas than that in microadenomas, the relative nyctohemeral variation of F was similar in these two groups. One month after operation, clinicl manifestations of macroadenomas significantly improved, but the number of these patients with significant blood ACTH decrease was significantly less than that in microadenomas. Conclusion Due to higher amount and automatism of ACTH secretion, increased blood F level induces variation of clinical characteristics and laboratorial findings in patients with macroadenoma compared to the patients with microadenoma.

A Case of Persistent Cushing's Syndrome

A case of persistent Cushing's syndrome in a 25 year-old male is presented. Inspite of bilateral total adrenalectomy twice during two years, there was no clinical improvement. Adrenal scanning revealed no adrenal remnants. ACTH secreting pituitary microadenoma is demonstrated by computed tomographic brain scan and hormonal studies. Selective transsphenoidal microadenomectomy results in clinical and endocrinological improvement.

A Case of Persistent Cushing's Syndrome

A case of persistent Cushing's syndrome in a 25 year-old male is presented. Inspite of bilateral total adrenalectomy twice during two years, there was no clinical improvement. Adrenal scanning revealed no adrenal remnants. ACTH secreting pituitary microadenoma is demonstrated by computed tomographic brain scan and hormonal studies. Selective transsphenoidal microadenomectomy results in clinical and endocrinological improvement.

Clinical Analysis of Functiononing Pituitary Adenoma

Forty-four patients were operated on functioning pituitary adenomas during 5 years since Jun. 1977 at the Department of Neurosurgery, Seoul National University Hospital. Clinical and laboratory findings were analyzed and the following results were obtained. 1) The peak incidence was in the 3rd and 4th decade 21 cases were male and 23 cases were female. 2) Endocrinologic study revealed prolactinoma in 28 cases(37%), somatotropic adenoma in 13 cases(17%), corticotropic adenoma in 3 cases(4%), endocrine-inactive adenoma in 32 cases(42%). 3) MAin symptoms were endocrine symptoms(86%), headache(75%) and visual field defect(59%). 4) Seven(16%) were in the stage I(micro-adenoma), 27(61%) in the stage II, 6(14%) in the stage III, 4(9%) in the stage IV. 5) The rate of endocrinologic cure or improvement was 65% in prolactinoma and 75% in somatotropic adenoma. This result was less favorable less favorable than the result of other recent studies, but it seemed to be due to large proportion of large or invasive adenoma instead of micro-adenoma in this series. 6) In prolactinoma, 7 out of 12 patients with amenorrhea resumed menstrual cycle and 2 patients had pregnancies postoperatively. 7) The visual field defect was improved in 16 of 21 cases(76%) postoperatively.