Effect of Cabergoline Treatment on Disease Control in Acromegaly Patients.

The aim of this study was to evaluate the efficacy of cabergoline in normalizing plasma IGF-I levels in acromegaly patients with elevated IGF-I levels after surgery and/or SRL therapy. Acromegaly patients (n: 143) were evaluated retrospectively. Patients with elevated IGF-I levels after surgery and/or SRLs therapy and a fixed dose of SRLs treatment for the last six months with no history of radiotherapy in the last three years were included in the study (n: 12). Previous treatment regimens, baseline PRL and IGF-I levels (ULNR), sella MRI, and immunohistochemical findings were evaluated. Cabergoline was used as an add on (n: 11) or single medical treatment (n: 1). The median duration of treatment with SRL alone was 12 months (range 6-48 months). The mean IGF-I value before cabergoline therapy was 1.45±0.4 ULNR. The mean cabergoline dose and duration of treatment were 1.55±0.75 mg/week and 9±6.3 months, respectively. IGF-I normalization was only achieved in patients with serum IGF-I concentration<1.5×ULNR before the onset of cabergoline treatment (n: 9). In some of the patients with IGF-I normalization, baseline prolactin levels were normal (n: 3). Immunopositivity for prolactin in adenoma tissue was found in three patients with IGF-I normalization. Cabergoline therapy is effective in the normalization of IGF-I levels even in normoprolactinemic acromegaly patients when IGF-I levels are mildly or moderately elevated during SRL therapy.

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.

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.

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.

The role of severity and duration of inflammation and hematological parameters on the outcome of subacute thyroiditis.

Background: The role of severity and duration of inflammatory findings on the development of persistent hypothyroidism and anemia has not been clarified in subacute thyroiditis (SAT). Methods: Demographic data and laboratory parameters of patients with SAT were analyzed retrospectively. Results: Permanent hypothyroidism was observed in 28.1% of patients. Baseline elevated erythrocyte sedimentation rate as defined >74.5 mm/h was found to be associated with permanent hypothyroidism, but the duration of inflammation was not different between the recovered and hypothyroid patients. Baseline hemoglobin values improved without specific therapy in 3.5 months. Conclusion: The initial severity but not the duration of inflammation increases the risk for the development of permanent thyroid dysfunction, and anemia improves with the resolution of inflammation.

[Box: see text].

Calciphylaxis: a report of six cases and review of literature.

Calciphylaxis is usually a fatal condition that develops in a few chronic renal failure patients, and it is characterized by calcifications in subcutaneous arteries, infarcts in skin, and the neighboring subcutis. Calciphylaxis, once considered as a rare condition, has been reported to have an annual incidence of 1% and a prevalence of 4% in dialysis patients. We describe our clinical experience in six end-stage renal disease patients on dialysis that presented with calciphylaxis and died due to sepsis, and review the pathogenesis, epidemiology, clinical and histopathologic features, and treatment of calciphylaxis. Physicians should initially consider the possibility of calciphylaxis in case of development of skin lesions in chronic renal failure patients with impaired calcium, phosphorus, and parathyroid hormone levels. The most important cause of mortality in this condition is infection. Therefore, differential diagnosis of these lesions from systemic vasculitis in their early stages and withdrawal of immunosuppressive therapy that increases the tendency to infections are essential.

Diagnosis and management of tumor-induced osteomalacia: a single center experience.

PURPOSE: The aim of this study is to review the clinical and laboratory characteristics, diagnostic and treatment modalities of tumor-induced osteomalacia (TIO) cases managed in a single center. MATERIAL METHODS: Demographic and clinical features, biochemical findings, diagnostic procedures, treatment modalities, and outcomes of nine patients who had the diagnosis of TIO were reviewed retrospectively. RESULTS: Mean age of the study group (F/M: 4/5) was 45.8 ± 10.8 years, and mean time from the onset of symptoms to diagnosis was 4.7 ± 2.8 years. The clinical manifestations were muscle weakness and difficulty in walking (8/9), hip pain (3/9), multiple fractures (2/9), stress fracture (2/9). Mean plasma phosphorus concentration was 1.28 ± 0.4 mg/dl at presentation. We performed radionuclide imaging modalities (18F-FDG PET/CT, Ga68-DOTATATE PET/CT, octreotide scintigraphy) in seven of nine patients, and tumor was detected in all. Lower extremity (n = 6; %67), head region (n = 2; %22) and thorax (n = 1; %11) were the tumor locations of our cases. Eight patients underwent surgery and remission was achieved postoperatively in all of the operated patients and plasma phosphorus level normalized in 4 ± 2 days. Pathological examination revealed mesenchymal tumors with different subtypes. Recurrence occurred in three patients at 13 ± 10.5 months after the first surgery. Two patients were reoperated and radiotherapy was also performed in one of them. CONCLUSION: Hypophosphatemia necessitates careful evaluation for the etiology. TIO is one of the important causes of adult-onset hypophosphatemic osteomalacia. Diagnosis of TIO is essential because the laboratory and clinical findings resolve after appropriate treatment.

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.

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.

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.

Female gonadal functions and ovarian reserve in patients with acromegaly: experience from a single tertiary center.

PURPOSE: To evaluate the gonadal functions and related factors in female patients with acromegaly at the time of diagnosis, the course of gonadal dysfunctions and pregnancies during the follow-up period, and the investigation of ovarian reserve with serum anti-Mullerian hormone (AMH) levels in patients with reproductive age. METHODS: Patients who were not menopausal at the time of acromegaly diagnosis (n = 47) were included in this study. Baseline gonadal status was evaluated retrospectively. Patients were divided into three groups: normal gonadal function (group 1), gonadal dysfunction without central hypogonadism (group 2), and central hypogonadism (group 3). Group 1 and group 2 were compared in terms of clinical and laboratory findings. AMH levels were studied in patients who were ≤ 45 years old (n = 14) at the time of the study. Data related to pregnancies (n = 13) were evaluated retrospectively. RESULTS: Group 1 included 18 patients (38%), group 2 included 18 patients (38%), and group 3 included 11 patients (24%). The estimated duration of acromegaly was longer, and baseline PRL levels were higher, in group 2 than group 1 (p = 0.002 and p = 0.015, respectively). Gonadal functions recovered in 66% of patients. AMH levels were low in 64% of patients. The frequency of maternal diabetes and hypertension was 7.7%, and there was no tumoral growth in any of the pregnancies. CONCLUSION: The most important factors affecting gonadal functions, excluding central hypogonadism, are hyperprolactinemia and the duration of the indolent period before diagnosis of acromegaly. AMH levels in the majority of patients were found to be lower than the expected age. Despite the decreased ovarian reserve, fertilization and normal birth can be achieved with careful surveillance.

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

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.

Vocal cord paralysis during the treatment of mantle cell lymphoma with vincristine.

CASE DESCRIPTION: We present a case of a seventy-eight year-old man who developed vocal cord paralysis without any sign of peripheral neuropathy during the treatment of Mantle Cell Lymphoma. He first presented in 2008 with a few bilateral small inguinal lymph nodes. Inguinal lymph node biopsy demonstrated Mantle Cell Lymphoma. Flow cytometry studies of peripheral blood and bone marrow cells were compatible with Mantle Cell Lymphoma. R-CHOP chemotherapy triweekly (Rituximab; Cyclophosphamide; Adriamycin; Vincristine; and Methylprednisolone) was planned. At the end of the second cycle, the patient complained of hoarseness without any symptoms of dysphagia or odynophagia. Direct flexible laryngoscopy showed bilateral vocal cord paralysis. Vincristine was discontinued and the patient's voice gradually resolved in about 4 months. CONCLUSION: Vincristine may cause peripheral, autonomic and cranial neuropathies. However cranial nerve involvement is quite uncommon.