Sema Ciftci Dogansen

Double benefit of long-acting somatostatin analogs in a patient with coexistence of acromegaly and ulcerative colitis

Somatostatin analogs control GH/IGF‐1 excess in acromegaly. Somatostatin receptors also mediate the complex effects of somatostatin on the gastrointestinal tract and may be defensive in inflammatory bowel diseases, such as ulcerative colitis. We present a patient who showed good response to long‐acting octreotide (OCT‐LAR) treatment in terms of both acromegaly and ulcerative colitis (UC).

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

PurposeTo 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).MethodsSomatotroph 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.ResultsSomatotroph 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.ConclusionBaseline hypointense somatotroph adenomas show a better response to SSA, whereas hypointensity was related to DA resistance in female prolactinomas.

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.

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 Crookes 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 Crookes 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.

Assessment of macroprolactinemia inpatients with prolactinoma

Abstract Purpose: Macroprolactin, the high-molecular mass prolactin isoform, is considered to be an inactive product with extrapituitary origin. Although macroprolactinemia is considered a benign condition, there is evidence of overlapping clinical features among patients with hyperprolactinemia. Data on the prevalence of macroprolactinemia in prolactinomas is also quite limited. The aim of this study was to assess the prevalence of macroprolactinemia in our patients with prolactinoma. Methods: The study included patients with macroprolactinoma (n=50) and microprolactinoma (n=16). Prolactin level was measured with an electrochemiluminescent immunoassay, and macroprolactinemia was defined as the percentage of prolactin recovery <40% after the polyethylene glycol precipitation. Results: Macroprolactinemia was not detected in our patients with prolactinoma (the percentage of PRL recovery range; 55%–96%). The mean percentage of prolactin recovery was similar in patients with macroprolactinoma and microprolactinoma (67.7%±8.0% and 70%±9.4%, respectively, p=0.96). Conclusion: Macroprolactinemia is generally associated with negative findings on pituitary imaging. Although the monomeric prolactin is dominant, rarely macroprolactin may also be present in prolactinomas. We did not detect presence of macroprolactin in any of the patients and there was no statistically significant difference between micro- and macroprolactinomas in terms of prolactin recovery.

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

PurposeTo 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.MethodsPatients 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.ResultsGroup 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.ConclusionThe 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.

The higher incidence of autoimmune thyroid disease in prolactinomas than in somatotrophinomas

OBJECTIVE Many studies have shown that prolactin (PRL) plays an important role in autoimmune diseases. The aim of this study was to compare the current frequency of autoimmune thyroid disease (ATD) in prolactinomas with another type of functional pituitary adenoma (FPA), somatotrophinoma. Another aim of the study was to evaluate possible factors related to thyroid autoimmunity and the process of ATD in FPAs. METHODS We retrospectively evaluated the presence of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) and thyroid morphologic findings in our patients with FPA (78 with acromegaly and 83 with prolactinoma). The relationship of autoantibody positivity with baseline PRL levels, activity of acromegaly, and treatment of dopamine agonists (DA) and hypogonadism was also assessed. Patients with ATD and hypothyroidism due to autoimmune thyroiditis were also evaluated. RESULTS ATD (Hashimotos thyroiditis) was detected more frequently in patients with prolactinoma than in patients with acromegaly (33% and 17%, respectively; p=0.01). Thyroid autoantibody positivity was found more frequently in females in the whole group (p=0.02) and in the acromegaly group (p=0.008). There was no difference according to sex among the patients with prolactinoma (p=0.800). ATD was found not to be related with baseline PRL levels, treatment of DA, and presence of hypogonadism (p=0.232, p=0.435, p=0.464, respectively) in the prolactinoma group, and activity of acromegaly, presence of hypogonadism in the acromegaly group (p=0.753, p=0.654, respectively). Autoimmune hypothyroidism was more frequent in the prolactinoma group than in the acromegaly group among patients with thyroid autoantibody positivity (p=0.004). CONCLUSION Thyroid autoantibodies should be evaluated both at the time of diagnosis and during the course of treatment in patients with prolactinoma, and thyroid function tests should be closely monitored in patients with autoantibody positivity.