The relationship between temporal muscle thickness and disease activity in Cushing's disease.

OBJECTIVE: This study aimed to investigate the relationship between hypercortisolism and temporal muscle thickness (TMT) in Cushing's disease (CD). METHODS: A retrospective review of medical records was conducted for patients with CD who presented to our clinic between 2012 and 2022. Biochemical data and TMT measurements from sella imaging were evaluated during diagnosis and the first postoperative year. RESULTS: A total of 44 patients were included in the study, with an average age of 43.9 years, of which 38 were female. The mean TMT at the time of diagnosis was 19.07 ± 1.71 mm, with no significant difference between males and females (p = 0.097), and no correlation between the TMT and age at diagnosis (p = 0.497). There was an inverse relationship between TMT and serum cortisol levels, 24-h UFC, and midnight salivary cortisol at the time of diagnosis of CD (p < 0.05, for all). One year after surgery, TMT significantly increased in all patients compared to baseline (p < 0.001). Furthermore, patients who achieved postoperative remission had significantly higher TMT values compared to those who did not achieve remission (p = 0.043). Among the patients who achieved remission, those who achieved remission through surgery had significantly higher TMT compared to those who could not reach remission with surgery and patients who started medical treatment and achieved biochemical remission (p = 0.01). Patients with severe myopathy and sarcopenia had significantly lower TMT values than the others (p < 0.001). CONCLUSION: Temporal muscle thickness was found to be associated with disease activity and disease control in Cushing's disease.

New radiological clues in the diagnosis of spindle cell oncocytoma of the adenohypophysis.

AIM: To present three new cases of spindle cell oncocytoma (SCO) from a single centre and to identify new radiological clues in the diagnosis of SCO according to the information obtained from the cases presented. MATERIALS AND METHODS: Three adults with SCO confirmed at histopathology were retrospectively reviewed. The medical records, imaging findings, operative notes, and histopathology findings for each patient were recorded. Magnetic resonance imaging (MRI) findings were evaluated, including tumour localisation, tumour size, signal intensity, imaging features on T1-weighted and T2-weighted images, and contrast enhancement characteristics. The study protocol was approved by the institutional review board. Informed consent was obtained from each patient. RESULTS: T1-weighted imaging (WI) and T2WI demonstrated millimetric hypointense foci and linear signal void areas in all lesions. Consistent with the hypervascular features of the tumour, intense contrast enhancement was observed during the early stages of dynamic contrast enhanced (DCE) MRI. Linear signal void areas showed contrast enhancement, but some of the hypointense millimetric foci remained without contrast enhancement. CONCLUSIONS: Although the radiological findings and preoperative diagnosis of SCO have been reported to be non-specific and impossible, respectively, in the literature, the characteristics of MRI and different patterns of contrast enhancement can help in recognising this rare entity. This article represents a single institution case series of SCOs and also includes the first description of a correlation of the histopathological findings with radiological findings and new clues in the differential diagnosis of SCOs. We described these new radiological clues as "Hasiloglu's Signs".

The problem of unrecognized acromegaly: surgeries patients undergo prior to diagnosis of acromegaly.

PURPOSE: To reveal the variety of symptoms experienced by patients before acromegaly diagnosis and to emphasize unneeded surgeries that patients undergo related to acromegaly prior to diagnosis of the disease. METHODS: In total, 490 consecutive adult patients with acromegaly who were treated at our institution between 1998 and 2014 were included in this cross-sectional study, of which 313 could be contacted. Participants were questioned about their complaints at initial consultation and at the time of diagnosis, the first medical professional who they consulted, interval between onset and diagnosis, and surgeries they had undergone. RESULTS: This study included 313 participants, of whom 181 were women. The mean age was 48.8 ± 12.0 years. Patients most frequently presented with acral growth of hands and feet (32.6%) and headache (26.2%). Internists were the medical specialists who were most frequently first consulted (29.4%) then neurosurgeons (11.8%). Acromegaly was generally diagnosed by endocrinologists (55%), followed by neurosurgeons (23%). The median elapsed period prior to diagnosis was 24 months, interquartile range 6.0-48.0 months. Some 45.7% had undergone surgery; 35.2% were related to acromegaly symptoms: head and throat surgery (12.8%), nose surgery (9.3%), thyroidectomy (6.4%), carpal tunnel surgery (4.8%). The delay period for patients who had an operation prior to acromegaly diagnosis was significantly longer than for those who had no operations (p < 0.001). CONCLUSIONS: Acromegaly patients mostly present to internal medicine professionals. Surgeries related to acromegaly complications and symptoms before diagnosis cause a long delay period before diagnosis. Medical staff must be more aware of the clinical aspects of acromegaly.

Extended endoscopic endonasal approach to the pterygopalatine fossa: anatomic study.

AIM: Our aim in this study was to recognize the endoscopic anatomy of the pterygopalatine fossa (PPF) and the anatomic variations of the related neurovascular structures, to define the endoscopic endonasal approach to this region. METHODS: Six fresh adult cadavers were studied (N=6) by endoscopic endonasal approach. To reach the pterygopalatine fossa endonasally, we performed the middle meatus transpalatine approach in 2 cadavers, the middle meatus transnasal approach in 2 cadavers and the inferior turbinatectomy transnasal approach in 2 cadavers. The superior and posterior walls of the maxillary sinus were defined and studied. The sphenopalatine foramen is widened by drilling the orbital process of the foramen and the sphenopalatine artery was exposed. The posterior wall of maxillary sinus was opened to expose the pterygopalatine fossa and its neurovascular contents, which were studied and documented. RESULTS: The PPF was easily approached by endoscopic transnasal transmaxillary approach. The PPF region was best exposed by the middle meatus tranasal approach. In the PPF; infraorbital nerve, vidian nerve, major palatine nerve, the infraorbital artery, internal maxillary artery, sphenopalatine artery, descending palatine artery, posterior superior alveolar artery and buccal artery were exposed. According Morton and Khan morphologic classification of the third portion of the internal maxillary artery we found intermediate type in 2 cadavers (33.3%), M' type in 2 cadavers (33.3%), T' type in 1 cadaver (16.7%) and Y' type in 1 cadaver (16.7%). Also, according to Chio and Park classification of the branching type of the infraorbital artery, posterior superior alveolar artery and deep palatine artery, we found type I in 4 cadavers (66%) and type II in 2 cadavers (33%). CONCLUSIONS: During the endoscopic transnasal transmaxillary approach to the PPF, it is possible to face wide range of variations in every phase of the approach. Understanding the anatomy of this region and the neurovascular relations from the endoscopic view by cadaver dissections will help us to performed more controlled and safe surgery.

Preoperative Somatostatin Analogue Treatment Might Trigger Apoptosis and Autophagy in Tumor Tissues of Patients with Acromegaly: A Pilot Study.

OBJECTIVE: To evaluate the effect of preoperative somatostatin analog (SRL) treatment on proteins associated with apoptosis and autophagy in patients with acromegaly and to determine factors correlating with these parameters. METHODS: Ex-vivo tumor samples of 11 SRL-treated and 9 SRL-untreated patients were retrospectively included in the study. Apoptotic and autophagic proteins were determined via immunohistochemical staining and apoptosis was evaluated via in situ DNA end labeling (TUNEL). RESULTS: TUNEL, caspase-3, and ATG-5 immunopositivity was significantly increased (p<0.01, p=0.01, p=0.01, respectively), survivin and beclin-1 immunopositivity was significantly decreased (p=0.03, p=0.02, respectively) in SRL-treated patients as compared with SRL-untreated controls. Ki-67 index was decreased significantly in the SRL-treated group (p=0.01). Significant positive correlations were detected between TUNEL and caspase-3 immunopositivity (r=0.577, p<0.01), and between survivin and beclin-1 immunopositivity (r=0.503, p=0.03). Age at diagnosis, preoperative GH, IGF-1 levels, tumor size, and invasion status were not found to affect TUNEL positivity nor did they correlate with caspase-3, survivin, beclin-1, ATG-5 immunopositivity (p>0.05 for all). Preoperative SRL treatment was the only factor that had a significant effect on TUNEL positivity (adjusted R2=0.39, p=0.02). Preoperative treatment duration was positively correlated with TUNEL and caspase-3 immunopositivity (r=0.526, p=0.02; r=0.475, p=0.04, respectively) and negatively correlated with survivin immunopositivity (r=-0.533, p=0.01). CONCLUSIONS: Somatostatin analog treatment might induce apoptosis, increase autophagy, and decrease cell proliferation in GH-secreting adenomas. Also, proteins related to cross-talk between autophagy and apoptosis are upregulated after SRL treatment.

Atherosclerotic risk factors and premature atherosclerosis in acromegaly before and after 48 months of octreotide-LAR treatment.

We studied premature atherosclerosis with carotid Doppler ultrasonography in active acromegaly before and after treatment. Patients (n = 27) with active acromegaly and 12 age-, gender-, and body mass index-matched healthy individuals were included in the study. Carotid intima-media thickness was decreased significantly in the inactive group after treatment (median: 0.6 mm, interquartile range [IQR]: 0.55-0.80]) when compared with the active group (median: 0.9 mm [IQR: 0.75-1.15], P < .0001), but there was no significant difference between the inactive and control groups. There was a correlation between homeostasis model of assessment-insulin resistance (P = .01, r = .41) and growth hormone (GH; P < .0001, r = .46). In conclusion, premature atherosclerosis was demonstrated in active acromegaly patients probably as a consequence of insulin resistance and direct vascular effects of GH and/or insulin-like growth factor 1.

Xanthomatous hypophysitis.

Xanthomatous hypophysitis (XH) is the rarely seen primary form of hypophysitis. The histological differential diagnosis includes other causes of hypophysitis, Erdheim-Chester disease (ECD), Langerhans cell histiocytosis, Rosai-Dorfman disease and plasma cell granulomas. We present a 39-year-old woman admitted to our department with headache, menstrual irregularity and galactorrhea. The MRI revealed a lesion with a central cystic/necrotic region and a diameter of almost 1cm. Histologic examination showed an inflammatory infiltrate of numerous foamy histiocytes, surrounding the necrotic tissue. On immunohistochemical sections, infiltrating foamy cells stained strongly positive for CD68, and negative for CD1a and S100. After establishing the diagnosis of XH, the patient underwent glucocorticoid treatment. XH should be considered in the differential diagnosis of pituitary lesions. Since XH is rare, it is difficult to assess the efficacy of medical/surgical treatment of this entity accurately.

Giant cell tumor of the frontal bone in an 18-month-old girl: a case report.

INTRODUCTION: Giant cell tumors (GCT) are benign, but locally aggressive primary bone neoplasms, that frequently occur in the epiphyses of the long bones. Less than 1% of all GCTs primarily involve the skull where they are preferentially seen in the sphenoid and temporal bones. In the pediatric age group they are exceptionally rare. CASE REPORT: The authors report the management of a GCT involving the frontal bone in an 18-month-old girl. The patient underwent wide surgical excision of the lesion and remains free of clinical and radiological evidence of tumoral recurrence thirty months after treatment. CONCLUSION: Although rare, GCTs should be taken into consideration as a differential diagnosis of rapidly enlarging cranial mass lesions in pediatric patients. Gross total surgical excision eliminates the potential risks of adjuvant radiotherapy. However, considering the aggressive nature and potential malignancy of these lesions, careful long-term clinical and imaging follow-up is recommended.

Recurrent Cushing's syndrome after adrenal autotransplantation.

Adrenalectomy with adrenal autotransplantation used to be performed frequently for Cushing's disease in the past because of the limitations of conventional radiological techniques and the lack of adequate neurosurgical techniques. Today, however, bilateral adrenalectomy may be still required for selective patients with Cushing's syndrome when partial hypophysectomy has failed to control hypercortisolism or the source for ectopic ACTH syndrome could not be determined. Here, we report a case of recurrent Cushing's syndrome due to a pituitary adenoma, who was treated with bilateral adrenalectomy and autotransplantation for her Cushing's syndrome. Having determined pituitary adenoma as the cause of recurrent Cushing's syndrome after endocrinological investigations and imaging, we were able to treat the patient with transsphenoidal adenomectomy. We suggest that transsphenoidal resection of the adenoma rather than excision of the autotransplants and adrenal remnants should be the preferred treatment method for recurrent Cushing's disease.

Pituitary tumour presenting with trigeminal neuralgia as an isolated symptom.

Invasion of the cavernous sinus by pituitary adenoma may cause involvement of cranial nerves III, IV, V and VI. However, trigeminal neuralgia as an isolated, initial symptom is very unusual. A patient with a pituitary adenoma, who had intractable trigeminal neuralgia as the only complaint which resolved following surgical removal is presented.

Prolactin-secreting carcinoma of the pituitary: clinicopathological and immunohistochemical study of a case with intracranial and intraspinal dissemination.

A 32-year-old female patient with a primary adenohypophyseal neoplasm that rapidly progressed to a fatal outcome is presented. The time interval between her admission to the hospital and her death was 3 months. Despite dopamine agonist therapy, local invasion as well as frontal and spinal cord metastases at Th 10-12 region developed, and four surgical resections were performed. The serum prolactin levels were high. Both the primary pituitary tumour and all the metastatic tumours had the same histological findings and immunohistochemical reactions. Each was composed of pleomorphic chromophobic cells with enlarged nuclei. Mitoses and necroses were frequent. Immunostains revealed prolactin in the tumour cells. A literature review revealed that in most of the pituitary carcinomas as in our case hyperprolactinaemia did not respond to medical therapy and the histopathological appearance of the tumour has not correlated with the aggressive behaviour of the tumour. It may therefore be considered that at least some of the cases with metastases in prolactin secreting pituitary carcinomas could be the result of hyperprolactinaemia itself.

Idiopathic granulomatous hypophysitis: are there reliable, constant radiological and clinical diagnostic criterias?

Idiopathic granulomatous hypophysitis is a rare inflammatory disease of unknown aetiology; few cases are reported. We review the clinical presentation and radiological characteristics of these cases and our own experience with three new surgical cases, to determine diagnostic criteria. MRI of three cases revealed sellar lesions extending into the chiasmatic cistern. Their shape varied, from dumbbell to spherical and elliptical. All were isointense with the brain on T1-weighted images and gave heterogeneously high signal on T2-weighted images. Contrast enhancement was homogeneous in one case and heterogeneous in another. The pituitary stalk could not be identified. There was no dural enhancement. The sphenoid sinus mucosa was thickened in two cases and normal in one.

Chiasmatic low-grade glioma presenting with sacral intradural spinal metastasis.

Leptomeningeal metastasis of low-grade gliomas in children has been documented in several series, both at the time of diagnosis and at relapse. The authors report a unique case of chiasmatic low-grade astrocytoma presenting with signs and symptoms related to the metastatic site rather than the primary site. In this respect, the possibility of appearance of symptoms and signs related to leptomeningeal dissemination preceding the signs and symptoms belonging to the primary site should be considered in this type of benign tumours.

Spontaneously regressing infundibular cyst: a case report.

A 74-year-old man reported headaches and blurring of vision for 1 month. MRI showed a nonenhancing infundibular cyst. Neurologic findings, blood and cerebrospinal fluid examinations, and chest and abdominal CT were all normal. MRI 4 months later showed no change. The patient was without any medication other than simple analgesics. One year later, the stalk had returned to its normal size and configuration on MRI.

The effect of prolactin and bromocriptine on human peripheral immune status.

The aim of this study was to determine the influence of elevated serum prolactin (PRL) levels on the peripheral lymphocyte subsets in patients with hyperprolactinemia. For this purpose we studied 20 hyperprolactinemic patient lymphocyte subsets by flow cytometry on their hyperprolactinemic state and after their serum prolactin concentration was normalized with bromocriptine (BC) alone or BC and surgery. We observed decreased absolute numbers and percentage of Natural Killer (p=0.0009 and 0.0001, respectively) and CD3/CD25 lymphocytes (p = 0.009 and 0.002) in hyperprolactinemic patients, compared to 8 sex- and age-matched normal controls. There was no correlation between PRL levels and CD16/56 and CD3/CD25 numbers (p=0.72 and 0.33, respectively). We did not find any significant difference in absolute numbers (p = 0.95) and percentage (p = 0.84) of B-lymphocytes of hyperprolactinemic patients, as compared with normal controls. We did not detect any increase in absolute cell numbers of CD16/CD56 (p = 0.21) and CD3/CD25 (p = 0.61) of BC-treated patients when compared to their hyperprolactinemic state. We demonstrated an increase in CD8-cells (p = 0.0173) and a decrease in CD4/CD8 ratio (p = 0.036) in hyperprolactinemic patients treated with BC. There was also an increase in the number of activated T-cells (CD3/HLA DR) in this group, compared to normal controls and the hyperprolactinemic state of the same patients (p = 0.04). In conclusion, elevated PRL levels do not lead to an "overstimulation" of the B-cells, but deteriorate the cytotoxic function.

Extradural balloon obliteration of the empty sella report of three cases (intrasellar balloon obliteration).

Empty sella syndrome is an anatomical and clinical entity composed of intrasellar reposition of the CSF and compression of the pituitary tissue, resulting in a clinical picture of headache, visual field defect, CSF rhinorrhea and some mild endocrinological disturbances. While some cases are primary with no appreciable aetiology, secondary cases are associated with prior operation or radiotherapy of the region. In our series, 3 patients with primary empty sella syndrome were treated by the current approach of extradural filling of the sellar cavity. This technique was first described by Guiot and widely accepted thereafter. We used a detachable silicon balloon filled with HEMA or liquid silicone for obliteration of the sellar cavity and obtained clinically satisfactory results without complications. Visual symptoms regressed and headache disappeared. But at long term follow-up all the balloons were found to be deflated. Despite the facility and efficacy of the technique we do not recommend it in the treatment of the empty sella because the filling of the sella is only transient and relapses may occur.

Meckel-Gruber syndrome.

Meckel-Gruber syndrome is a congenital disorder characterized by occipital encephalocele, polydactyly and polycystic kidneys. This rare syndrome has been reported in the literature as incompatible with life. We present the case of a newborn afflicted with the clinical triad of Meckel-Gruber syndrome. Appropriate treatment instituted in our case led to a good early outcome.