Promising Outcomes in Acromegaly Patients Receiving CyberKnife Stereotactic Hypofractionated Radiotherapy.

BACKGROUND: The primary treatment for patients with acromegaly has traditionally been transsphenoidal surgery, with decreasing reliance on radiotherapy (RT) due to advancements in pharmacotherapy (PT). Despite these advancements, a substantial portion of patients still face persistent acromegaly, necessitating novel treatment approaches. This study investigates the role of CyberKnife Stereotactic Hypofractionated Radiotherapy (CK-HFRT) in persistent acromegaly. OBJECTIVE: The primary objective was to assess the impact of CK-HFRT on endocrine remission (ER) rates while maintaining acceptable toxicity levels. METHODS: The study retrospectively analyzed 31 consecutive patients with acromegaly who received CK-HFRT following multiple unsuccessful surgeries and prolonged PT without ER. Various CK-HFRT dose fractionation regimes were administered, and dose volume histograms were evaluated. Tumor control, cured disease (CD), endocrine remission (ER) rates, and overall survival were estimated at a median follow-up of 62 months. Acute and late toxicity, including pituitary insufficiency and radiation-induced optic neuropathy (RION), were also assessed. RESULTS: At 62 months of follow-up, the study group demonstrated excellent tumor control with 100% nonprogressive adenomas. Endocrine remission was achieved in 86.7% of patients, with a 22.4% CD rate at five years. Pituitary insufficiency occurred in 32.3% of patients, and no cases of RION were reported. The study observed three deaths related to cardiovascular diseases, all in patients receiving PT. Overall survival at five years was 79.2%. CONCLUSION: CyberKnife stereotactic hypofractionated radiotherapy, as an adjunct to PT, provides a viable treatment option for patients with persistent acromegaly following unsuccessful surgeries. The therapy results in substantial ER rates and tumor control while minimizing the risk of permanent radiation-induced optic neuropathy. However, the decision to administer CK-HFRT should be individualized, considering the patient's overall condition and treatment history.

Evaluation of pulmonary side effects in prolactinoma patients treated with cabergoline.

INTRODUCTION: Cabergoline (CAB) is the most used dopamine agonist in the treatment of prolactinomas. Studies related to the treatment of Parkinson's disease have shown that dopamine agonists can lead to fibrotic syndromes affecting the heart and the lung. The aim of this study was to evaluate the possible pulmonary side effects of CAB in prolactinoma patients. MATERIAL AND METHODS: Chest X-ray imaging and pulmonary function parameters like forced vital capacity (FVC), total lung capacity (TLC), and diffusion capacity for carbon monoxide (DLCO) were evaluated in 73 prolactinoma patients. The cumulative dose of CAB and the total duration of CAB use were also calculated, and all data were reviewed retrospectively. RESULTS: The median cumulative CAB dose was 192 mg, and the median duration of CAB use was 64 months. Only 13 patients (17%) among this cohort had abnormal DLCO results that could be an indirect sign of pulmonary fibrosis. These abnormal DLCO results were found not to be associated with cumulative CAB dose in these 13 patients. CONCLUSIONS: CAB appears to be safe in terms of pulmonary functions with a median cumulative dose of 192 mg in prolactinoma patients.

Frequency of hyperostosis frontalis interna in patients with active acromegaly: is there a possible role of GH excess or hyperprolactinemia in its etiopathogenesis?

PURPOSE: Acromegaly is characterized by bone changes due to excessive growth hormone (GH) secretion. Hyperostosis frontalis interna (HFI) is described as an overgrowth in the inner plate of the frontal bone. An increased incidence of HFI has been reported in patients with acromegaly. Since the etiology of HFI is poorly understood, we have analyzed whether there is a relationship between the hormonal and metabolic status of patients with acromegaly (with or without hyperprolactinemia) and the pathogenesis of HFI. METHODS: Forty-five patients with acromegaly and two control groups consisting of 25 patients with prolactinoma (group 1) and 47 healthy subjects (group 2) were included in this retrospective study. Baseline hormonal data and cranial imaging were obtained from medical records and analyzed. RESULTS: Mean frontal bone thickness was 6.75 mm in acromegaly, 4.85 mm in group 1, and 5.1 mm in group 2 of controls (p < 0.001). The frequency of HFI was higher in acromegalic patients than in the controls (22%, 0%, and 2.2%, respectively). There was no difference between the HFI positive and negative acromegalic patients in basal GH, IGF-1, and PRL levels, IGF-1 index, diagnosis lag time, and insulin resistance. There was no difference between groups regarding parietal and occipital bone thickness. CONCLUSION: Although the frequency of HFI is 22% in patients with acromegaly, neither excess GH nor hyperprolactinemia plays a role in its etiopathogenesis. Various genetic or epigenetic factors may contribute to its etiology.

The Importance of DHEA-S Levels in Cushing's Syndrome; Is There a Cut-off Value in the Differential Diagnosis?

The purpose of this study was to determine possible cut-off levels of basal DHEA-S percentile rank in the differential diagnosis of patients with Cushing's syndrome (CS) with ACTH levels in the gray zone and normal DHEA-S levels. In this retrospective study including 623 pathologically confirmed CS, the DHEA-S percentile rank was calculated in 389 patients with DHEA-S levels within reference interval. The patients were classified as group 1 (n=265 Cushing's disease; CD), group 2 (n=104 adrenal CS) and group 3 (n=20 ectopic ACTH syndrome).ROC-curve analyses were used to calculate the optimal cut-off level of DHEA-S percentile rank in the reference interval in the differential diagnosis of CS, and the effectiveness of this cut-off level in the identification of the accurate etiology of CS was assessed in patients who were in gray zone according to their ACTH levels. The DHEA-S percentile rank in the reference interval were significantly lower in group 2 compared to the other two groups (p<0.001), while group 1 and group 3 had similar levels. The optimal cut-off level of DHEA-S percentile rank in the reference interval providing differential diagnosis between group 1 and group 2 was calculated as 19.5th percentile (80.8% sensitivity, 81.5% specificity) and the level demonstrated the accurate etiology in 100% of CD and 76% of adrenal CS patients who were in the gray zone. This study showed that the cut-off value of DHEA-S level less than 20% of the reference interval could be used for differential diagnosis of CD and adrenal CS with high sensitivity and specificity, and it should be taken into the initial evaluation.

Optimal testosterone level to improve symptoms of hypogonadism without causing dopa-testotoxicosis in male macroprolactinoma.

BACKGROUND: Male prolactinoma treatment by dopamine agonists (DA) restores sexual function. However, excessive DA dose can lead to impulse control disorder. OBJECTIVES: The aim of this retrospective study was to determine the level of testosterone that eliminates symptoms and provides fertility in male macroprolactinoma, without causing these adverse effects. MATERIALS AND METHODS: Twenty-seven male patients with macroprolactinoma were included. There were 16 macro (≥1-2.8cm), 7 large macro (≥2.9-3.9cm) and 4 giant (≥4cm) adenomas. Prolactin (PRL) and testosterone (T) levels were evaluated. A timeline was created to analyze improvement in symptoms of hypogonadism and infertility. Testosterone levels were compared with age-matched controls. RESULTS: Mean PRL, basal tumor diameter and shrinkage were 2846±3415ng/mL, 27.2±10.2mm and 63.4%, respectively. Basal T levels were 1.6±1.0ng/mL for patients and 4.4±1.5ng/mL for controls (P<0.001). Mean T level in the asymptomatic period was significantly lower than in controls (3.2±0.4ng/mL vs. 4.4±1.5ng/mL, respectively; P=0.002), while mean PRL was 27.2ng/mL. Fertility was achieved in 6 of the patients seeking fertility, and there was no difference in T level between these patients and controls (3.7±0.8ng/mL and 4.4±1.5ng/mL, respectively; P=0.14); when fertility was achieved, mean PRL was 26.9±23ng/mL. CONCLUSION: Patients should be carefully questioned regarding complaints at each consultation, and DA dose should not be increased unnecessarily, to avoid possible serious adverse effects.

Serologic Testing for Celiac Disease in Graves' Hyperthyroidism: Should We Act Early?

BACKGROUND: The general practice is to screen patients with autoimmune thyroid disease for celiac disease (CD); however, optimal timing for CD screening for patients with Graves'Disease (GD) has not been identified yet. The aim of the study was to show whether positive celiac antibodies persist after euthyroidism is achieved. MATERIALS AND METHODS: Serum samples were collected from 35 patients with GD (23 female and 12 male) who applied to the endocrine outpatient clinic. Patients and healthy controls were screened for CD with IgG and IgA antigliadin antibodies (IgG - AGA and IgA - AGA), IgA endomysial antibody (IgA-EMA) and IgA tissue transglutaminase antibody (IgA anti-tTG). These antibodies were reevaluated when patients were euthyroid under antithyroid therapy. Small intestine biopsy was offered to the patients who remained antibody positive after being euthyroid. RESULTS: Screening 35 patients with GD revealed positive results for IgA-AGA (n = 6/35, 17%), IgG-AGA (n = 9/35, 26%), IgA-EmA (n = 2/35, 6%) and IgA-tTG (n = 2/35, 6%). No patient had multiple antibodies positive. Selective IgA deficiency was not detected in patients and controls. When patients were euthyroid, baseline positive IgA-AGA, IgG-AGA, and IgA-EmA became negative, while positive anti-tTG persisted in two patients. Endoscopic duodenal biopsy showed a normal villi/crypts ratio in these patients. None of the controls had positive antibodies. CONCLUSION: Due to possibility of false seropositivity of celiac antibodies in patients with Graves' thyrotoxicosis, one should defer testing for CD until euthyroidism has been achieved.

A single-center experience of transsphenoidal endoscopic surgery for acromegaly in 73 patients: results and predictive factors for remission.

BACKGROUND: Transsphenoidal endoscopic surgery is the first-line treatment for growth hormone-secreting adenomas. OBJECTIVE: To analyse the results of the transsphenoidal endoscopic approach for acromegaly and to determine the predictive factors of remission. METHODS: A single-centre retrospective review was performed in patients who underwent endoscopic transsphenoidal surgery for acromegaly between January 2009 and January 2019. Demographic features, clinical presentation, histopathology records, complications and pre- and postoperative radiologic and endocrinological assessments were evaluated. The factors that influenced the remission rates were investigated. RESULTS: A total of 73 patients underwent surgery via the transsphenoidal endoscopic approach. Cavernous sinus invasion was detected in 32 patients (43.8%); and macroadenoma, in 57 (78%). The pathology specimens of the 27 patients (36.9%) showed dual-staining adenomas with prolactin. A total of 51 patients (69.8%) attained biochemical remission 1 year after surgery. A second operation was performed in 10 patients (13.6%) with residual tumours without biochemical remission in the first year. Six (60%) of the patients attained remission at the last follow-up. Transient diabetes insipidus was observed in 18 patients (24.6%); and rhinorrhoea, which was resolved with conservative treatment, in 4 (5.4%). None of the patients developed panhypopituitarism. The presence of cavernous sinus invasion and preoperative IGF-1, immediate postoperative GH and third-month IGF-1 levels were predictive of remission. CONCLUSION: Transsphenoidal endoscopic surgery is a safe and effective treatment for acromegaly. Reoperation should be considered in patients with residual tumours without remission.

Outcomes of Patients with Macroprolactinoma Desiring Pregnancy: Follow-Up to 23 Years from a Single Center.

Macroprolactinomas are rarely seen in women, and pregnancy is a risk factor for tumor growth. More studies are needed to determine appropriate management for macroprolactinoma and pregnancy. The aim of our study is to evaluate effects of treatment with dopamine agonists on macroadenoma before and during pregnancy, safety of dopamine agonists on fetus, post-pregnancy prognosis and long-term results. This is a single center retrospective study. Thirty-four pregnancies occurred in 21 patients under medical therapy. Prolactin levels, treatment results, tumor diameter changes, maternal-fetal outcomes, and disease activity were evaluated. The median tumor size at the time of diagnosis was 15 mm (10-28). Residual adenoma diameter was smaller in those receiving medical therapy longer than one year till the conception (p=0.047). Treatment was discontinued in 28 pregnancies after pregnancy confirmation, and 6 patients were exposed to bromocriptine throughout pregnancy. There was no symptomatic tumor growth during gestation. Among 27 live births, none of the fetuses developed neonatal malformation except for a case of Down syndrome. While early remission rate after pregnancy was 9.5%, this rate reached 33.3% at last follow-up visit. Lowered PRL levels at postpartum period (p=0.040), smaller tumor size at last follow-up visit (p=0.030), and total disappearance of tumor (p=0.026) were the contributor factors for remission. Use of dopamine agonist over one year may reduce the risk of symptomatic tumor growth during pregnancy in patients without invasive or large macroprolactinoma before pregnancy. Exposure to dopamine agonists seems generally safe for the fetus.

Disease Activity May Not Affect the Prognosis of Coexisting Thyroid Cancer in Acromegalic Patients.

Acromegaly is known to be associated with high incidence of malignancies probably due to the mitogenic effects of IGF-1. Differentiated thyroid cancer (DTC) is reported to be one of the most frequent malignancies associated with acromegaly. But there is no data about the clinical course of DTC in acromegalic patients. In this study, we evaluated the course of DTC in 14 acromegalic patients retrospectively. Fourteen papillary thyroid cancer patients without acromegaly, who were matched with the acromegalic patient group for age, gender and properties of thyroid cancer, were investigated as the control group. We identified no change in the course and treatment responses of DTC in association with the acromegaly activity, gender, age and disease duration, and all patients were found to be in remission for DTC at the time of investigation. Retrospective analysis of this cohort suggests that the activity of acromegaly may not affect the treatment responses and prognosis of coexisting DTC.

Dopamine Agonist-Induced Impulse Control Disorders in Patients With Prolactinoma: A Cross-Sectional Multicenter Study.

CONTEXT: Dopamine agonist (DA)-induced impulse control disorder (ICD) in patients with prolactinomas is not sufficiently known. OBJECTIVE: To evaluate the prevalence of DA-induced ICDs and possible risk factors related to these disorders in patients with prolactinoma. DESIGN, SETTING, AND PARTICIPANTS: This is a cross-sectional multicenter study involving 308 patients with prolactinoma followed up in tertiary referral centers who received at least three months of DA therapy. DA-induced ICDs (pathological gambling, hypersexuality, compulsive shopping, and compulsive eating) and impulsivity were assessed using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson Disease and the Barratt Impulsiveness Scale-11, respectively. Patients were evaluated in terms of parameters related to ICD development. RESULTS: Any ICD prevalence was 17% (n = 51). Hypersexuality was most common (6.5%). Although any ICD and hypersexuality were more common in male patients (P = 0.009, P < 0.001, respectively), compulsive eating was more common in female patients (P = 0.046). Current smoking, alcohol use, and gambling history were more frequent (P = 0.033, P = 0.002, P = 0.008, respectively) in patients with any ICD. In Barratt Impulsiveness Scale-11 total, attentional, motor, and nonplanning scores were higher in patients with any ICD (P < 0.001). Current smoking and alcohol use were more frequent (P = 0.007, P = 0.003, respectively) and percentage increase of testosterone levels at last visit was higher (P = 0.021) in male patients with prolactinomas with hypersexuality. CONCLUSION: Any ICD may be seen in one of six patients with prolactinoma who are receiving DA therapy. Endocrinology specialists should be aware of this side effect, particularly in male patients with a history of gambling, smoking, or alcohol use.

Three Novel MEN1 Variants in AIP-Negative Familial Isolated Pituitary Adenoma Patients.

OBJECTIVES: Pituitary adenomas (PAs) may rarely occur in well-defined hereditary conditions, like multiple endocrine neoplasia type 1 (MEN1) syndrome and familial isolated pituitary adenoma (FIPA) associated with germline mutations in MEN1 and AIP, respectively. This study aimed to assess MEN1 genetic abnormalities in AIP mutation-negative FIPA patients, not associated with MEN1 components. METHODS: Among 20 patients evaluated in 13 FIPA families, 12 were previously reported as AIP mutation-negative. In this study, 6 new families with 8 patients were recruited. All patients were subjected to multiplex ligation-dependent probe amplification to detect copy number variations in AIP and MEN1, and AIP sequencing was performed in additional patients. AIP mutation-negative patients were subjected to MEN1 sequencing. RESULTS: Our cohort revealed only 3 novel heterozygous MEN1 variants including c.1846T>A p.(*616Argext*21), rs778272737:T>C, and rs972128957:C>T in 2 families, with patients diagnosed with Cushing disease, nonfunction al adenoma, and acromegaly, respectively. Among them, c.1846T>A p. (*616Argext*21) is a stop codon read-through, whereas the others are 3'UTR variations. MEN1 variation frequency was detected as 15%. CONCLUSIONS: MEN1 alterations can be of significance in FIPA patients and screening could be offered to AIP mutation-negative patients without MEN1 features. Further studies are needed to clarify the role of MEN1 in FIPA patients.

Evaluation of the natural course of thyroid nodules in patients with acromegaly.

PURPOSE: To investigate the nodular thyroid disease (NTD) and the natural course of thyroid nodules in patients with acromegaly. METHODS: 138 patients with acromegaly (73 F/65 M), whose initial thyroid ultrasonography performed in our university hospital, were included in this study. The frequencies of NTD, papillary thyroid cancer (PTC) and associated factors on nodule formation were investigated at initial assessment. Patients who had NTD continued to follow-up (n = 56) were re-evaluated with a ultrasonography performed after a mean 7-years follow-up period. The nodule size changes were compared with the initial data and the factors affecting nodule growth were investigated. RESULTS: The frequency of NTD was found 69%. Patients with NTD were older (p = 0.05), with higher baseline IGF-1%ULN (upper limit of normal) (p = 0.01). In patients with NTD, the majority had similar nodule size (45%), decreased nodule size in 30% and nodule growth in 25%. In patients with active acromegaly at last visit, nodule growth was more significant (p < 0.001). For one unit change in the IGF-1 levels, nodule growth increased by 1.01 folds and presence of active acromegaly disease was related with ninefolds increase in nodule growth. The frequency of PTC was 14% in patients with nodule growth and PTC was diagnosed 11% of all acromegalic patients. CONCLUSION: Both NTD and nodule growth is more frequent in active acromegalic patients. Thyroid nodules may show dynamic changes according to the disease activity and nodule growth should be closely monitored due to the risk of malignancy in patients with active acromegaly disease.

Clinical Significance of Granulation Pattern in Corticotroph Pituitary Adenomas.

OBJECTIVE: The granulation pattern of pituitary tumors may be important to predict tumor behavior, treatment outcomes, and recurrences. Therefore, we compared densely granulated corticotroph tumor (DGCT) and sparsely granulated corticotroph tumor (SGCT) in terms of clinicopathologic findings. MATERIAL AND METHOD: A total of 41 patients (31 females/10 males) were assessed in the study. The granulation patterns were detected by Periodic Acid-Schiff (PAS) and adrenocorticotropic hormone (ACTH) immunoreactivity. Diffuse and strong staining by PAS and ACTH were identified as DGCT, whereas faint staining by PAS and focal, weak staining by ACTH were identified as SGCT. Perinuclear ring-like patterns with low molecular weight keratin were identified as Crooke's cell tumors. DGCTs and SGCTs were compared in terms of clinical findings and treatment outcomes. RESULTS: The majority of the patients (71%) had DGCTs (n=29); whereas 24% of the patients had SGCTs (n=10) and 5% of the patients had Crooke's cell tumors (n=2). DGCTs and SGCTs were similar in terms of age, sex, estimated duration of disease, baseline cortisol and ACTH levels. SGCTs were larger than DGCTs (p=0.034). The remissions with surgery rates were similar between the groups; however, hypothalamic-pituitaryadrenal axis recovery time was longer in SGCTs (p=0.033). Persistent disease after surgery was slightly higher in DGCTs and recurrences were frequent in SGCTs; however, the differences were not statistically significant. CONCLUSION: DGCTs are often small microadenomas, while SGCTs are larger. Recurrences were slightly more common in SGCTs; however, further studies including larger series are needed to be able to obtain more significant results.

Screening of AIP Gene Variations in a Cohort of Turkish Patients with Young-Onset Sporadic Hormone-Secreting Pituitary Adenomas.

Aims: Aryl hydrocarbon receptor-interacting protein (AIP) gene mutations have long been associated with apparently sporadic pituitary adenomas (PAs) with a prevalence range of 0-12%. The aim of this study was to evaluate the frequency of germline AIP variations in a large cohort of apparently sporadic PAs diagnosed before the age of 40 years, who did not exhibit hypercalcemia and/or MEN1 syndrome components during long-term follow-up. Materials and Methods: A total of 97 patients, diagnosed with functional PAs ≤40 years old, composed of somatotropinoma (n = 55), prolactinoma (n = 25), and corticotrophinoma (n = 17), were recruited for this study. Fifty-one of these patients [somatotropinoma (n = 30), prolactinoma (n = 15), and corticotrophinoma (n = 11)] were previously reported as AIP mutation-negative by Sanger sequencing. The entire coding sequence of the AIP gene, along with exon/intron boundaries and the untranslated regions of 41 newly recruited patients, were sequenced for germline variations. In addition, all patients were subjected to multiplex ligation-dependent probe amplification to detect copy number variations in the AIP gene. Results: The AIP c.911G>A: p.Arg304Gln (rs104894190) variant was detected in only two patients with functional PA: one with somatotropinoma [in 1/55 (1.8%)] and one with prolactinoma [in 1/25 (4%)]. None of the corticotrophinomas revealed AIP gene alterations. Thus, the overall prevalence of AIP variation was 2.1% in our cohort. Conclusions: Germline AIP gene variations among Turkish patients with apparently sporadic PAs are relatively rare among patients ≤40 years old. None of the patients in our cohort revealed any obviously pathogenic AIP variants.

Predictors of colonic pathologies in active acromegaly: single tertiary center experience.

BACKGROUND: Regarding the incidence of colorectal malignancy and polyps in patients with acromegaly, studies reported different results in different populations. For this reason, the aim of this study was to determine the frequency of possible colonic pathologies, such as diverticula, polyps, and malignancies in Turkish patients with active acromegaly and factors affecting them. METHODS: A total of 134 patients with acromegaly and 134 patients with irritable bowel syndrome/dyspeptic symptoms as a control group were included in the study. None of these patients had a previous or family history of colonic neoplasms. Colonoscopies of patients with acromegaly were performed before definitive surgery in a single center by experienced endoscopists. RESULTS: The acromegaly and control groups were similar in terms of age and sex. The incidence of all colonic polyps was significantly higher in the acromegaly group (p = 0.012). The frequency of hyperplastic polyps was also increased in the acromegaly group (p = 0.004); however, the frequencies of adenomatous polyps and colonic diverticula were similar in both groups. In the comparison of patients with acromegaly for the presence of polyps, those with polyps were older, had higher levels of insulin-like growth factor (IGF-1), were of male sex, and skin tags were more common (p = 0.016, p = 0.034, p = 0.006 and p = 0.001, respectively). There were no colorectal malignancies in the patients with active acromegaly. CONCLUSION: The frequency of hyperplastic polyps was increased, whereas colonic malignancy was not observed in Turkish patients with active acromegaly.

Dynamic changes of central thyroid functions in the management of Cushing's syndrome.

OBJECTIVE: The aim of this study was to determine the frequency of central thyroid dysfunctions in Cushing's syndrome (CS). We also aimed to evaluate the frequency of hyperthyroidism due to the syndrome of the inappropriate secretion of TSH (SITSH), which was recently defined in patients with insufficient hydrocortisone replacement after surgery. MATERIALS AND METHODS: We evaluated thyroid functions (TSH and free thyroxine [fT4]) at the time of diagnosis, during the hypothalamo-pituitary-adrenal axis recovery, and after surgery in 35 patients with CS. The patients were separated into two groups: ACTH-dependent CS (group 1, n = 20) and ACTH-independent CS (group 2, n = 15). Patients' clinical and laboratory findings were evaluated in five visits in the outpatient clinic of the endocrinology department. RESULTS: The frequency of baseline suppressed TSH levels and central hypothyroidism were determined to be 37% (n = 13) and 26% (n = 9), respectively. A negative correlation was found between baseline cortisol and TSH levels (r = -0.45, p = 0.006). All patients with central hypothyroidism and suppressed TSH levels showed recovery at the first visit without levothyroxine treatment. SITSH was not detected in any of the patients during the postoperative period. No correlation was found between prednisolone replacement after surgery and TSH or fT4 levels on each visit. CONCLUSION: Suppressed TSH levels and central hypothyroidism may be detected in CS, independent of etiology. SITSH was not detected in the early postoperative period due to our adequate prednisolone replacement doses.

Impact of Glucose Metabolism Disorders on IGF-1 Levels in Patients with Acromegaly.

In this study, we aimed to evaluate the presence of glucose metabolism abnormalities and their impact on IGF-1 levels in patients with acromegaly. Ninety-three patients with acromegaly (n=93; 52 males/41 females) were included in this study. Patients were separated into three groups such as; normal glucose tolerance (n=23, 25%), prediabetes (n=38, 41%), and diabetes mellitus (n=32, 34%). Insulin resistance was calculated with homeostasis model assessment (HOMA). HOMA-IR > 2.5 or ≤2.5 were defined as insulin resistant or noninsulin resistant groups, respectively. Groups were compared in terms of factors that may be associated with glucose metabolism abnormalities. IGF-1% ULN (upper limit of normal)/GH ratios were used to evaluate the impact of glucose metabolism abnormalities on IGF-1 levels. Patients with diabetes mellitus were significantly older with an increased frequency of hypertension (p<0.001, p=0.01, respectively). IGF-1% ULN/GH ratio was significantly lower in prediabetes group than in normal glucose tolerance group (p=0.04). Similarly IGF-1% ULN/GH ratio was significantly lower in insulin resistant group than in noninsulin resistant group (p=0.04). Baseline and suppressed GH levels were significantly higher in insulin resistant group than in noninsulin resistant group (p=0.024, p<0.001, respectively). IGF-1% ULN/GH ratio is a useful marker indicating glucose metabolism disorders and IGF-1 levels might be inappropriately lower in acromegalic patients with insulin resistance or prediabetes. We suggest that IGF-1 levels should be re-evaluated after the improvement of insulin resistance or glycemic regulation for the successful management of patients with acromegaly.

Dynamic changes of central thyroid functions in the management of Cushing's syndrome

ABSTRACT Objective The aim of this study was to determine the frequency of central thyroid dysfunctions in Cushing's syndrome (CS). We also aimed to evaluate the frequency of hyperthyroidism due to the syndrome of the inappropriate secretion of TSH (SITSH), which was recently defined in patients with insufficient hydrocortisone replacement after surgery. Materials and methods We evaluated thyroid functions (TSH and free thyroxine [fT4]) at the time of diagnosis, during the hypothalamo-pituitary-adrenal axis recovery, and after surgery in 35 patients with CS. The patients were separated into two groups: ACTH-dependent CS (group 1, n = 20) and ACTH-independent CS (group 2, n = 15). Patients' clinical and laboratory findings were evaluated in five visits in the outpatient clinic of the endocrinology department. Results The frequency of baseline suppressed TSH levels and central hypothyroidism were determined to be 37% (n = 13) and 26% (n = 9), respectively. A negative correlation was found between baseline cortisol and TSH levels (r = -0.45, p = 0.006). All patients with central hypothyroidism and suppressed TSH levels showed recovery at the first visit without levothyroxine treatment. SITSH was not detected in any of the patients during the postoperative period. No correlation was found between prednisolone replacement after surgery and TSH or fT4 levels on each visit. Conclusion Suppressed TSH levels and central hypothyroidism may be detected in CS, independent of etiology. SITSH was not detected in the early postoperative period due to our adequate prednisolone replacement doses.

Clinicopathological significance of baseline T2-weighted signal intensity in functional pituitary adenomas.

PURPOSE: To assess baseline T2-weighted signal intensity (T2-WSI) of functional pituitary adenomas (FPA), and to investigate the relationship of baseline T2-WSI with clinical features, histopathological granulation patterns, and response to treatment in patients with acromegaly, prolactinoma and Cushing's disease (CD). METHODS: Somatotroph adenomas (n = 87), prolactinomas (n = 78) and corticotroph adenomas (n = 29) were included in the study. Baseline T2-WSI findings (grouped as hypo-, iso- and hyperintense) were compared with hormone levels, tumor diameter, granulation patterns and response to treatment. RESULTS: Somatotroph adenomas were mostly hypointense (53%), prolactinomas were dominantly hyperintense (55%), and corticotroph adenomas were generally hyperintense (45%). Hyperintense somatotroph adenomas were larger in size with sparsely granulated pattern and tumor shrinkage rate was lower after somatostatin analogues (SSA) (p = 0.007, p = 0.035, p = 0.029, respectively). T2 hypointensity was related with higher baseline IGF-1% ULN (upper limit of normal) levels and a better response to SSA treatment (p = 0.02, p = 0.045, respectively). In female prolactinomas, hyperintensity was correlated with a smaller adenoma diameter (p = 0.001). Hypointense female prolactinomas were related to younger age at diagnosis, higher baseline PRL levels and dopamine agonist (DA) resistance (p = 0.009, p = 0.022, p < 0.001, respectively). Hyperintense corticotroph adenomas were related to larger adenoma size and sparsely granulated pattern (p = 0.04, p = 0.017, respectively). There was no significant difference in the recurrence with T2WSI in CD. CONCLUSION: Baseline hypointense somatotroph adenomas show a better response to SSA, whereas hypointensity was related to DA resistance in female prolactinomas.