Seher Tanrikulu

A rare case: Shwachman–Diamond syndrome presenting with diabetic ketoacidosis

Dear Sir, Shwachman–Diamond syndrome (SDS) is a rare autosomal recessive multi-system disease that usually manifested with exocrine pancreatic insufficiency, short stature, and chronic neutropenia [1]. Previously only a few SDS patients have been reported to develop diabetes [2]. We report a case of SDS with diabetic ketoacidosis and osteopenia in which mutations of the SDS gene have been identified. A 29 year old woman was admitted to emergency room with symptoms of frequent urination and confusion. For the last 15 days, her oral intake was not satisfactory because she had nausea and vomiting. She had no history of diabetes mellitus or any other disease. On her examination, she had no orientation and cooperation. She appeared dehydrated and her mouth and mucosas were dry. Lab findings were as follows: Hg: 15.5/ll, WBC: 1200/ll (NEU: 100/ll), glucose: 483 mg/dl, BUN: 25 mg/dl, creatinine: 1.46 mg/dl, potassium: 1.7 mEq/l, total protein: 5.5 g/dl, albumin: 2.2 g/dl, calcium: 5.6 mg/dl, phosphorus: 0.1 mg/dl, pH: 6.94, and HCO3: 4.3 mmol/l. At urinalysis, ketonuria was ?3 and glucosuria was ?4. Her clinical and laboratory findings were consistent with diabetic ketoacidosis. Patient was treated with iv fluid and electrolyte replacement and insulin infusion. Her body mass index was calculated as 27.5 kg/m. 25 OH vit D was 6 ng/ml and PTH was 99 pg/ml. Her HbA1c was 11.4%, C-peptide was 1.8 (0.4–4), and anti-insulin antibody was positive. After these findings, the patient was investigated for malnutrition. Stool analysis revealed rare protein fibers. Her serum amylase and lipase were determined at relatively lower levels. Because she had hypocalcemia and hypophosphatemia, DEXA was performed and osteopenia (L2 T score: -1.65, Z score: -1.63 and trochanter of femur T score: -2.29, Z score: -1.95) was detected. Pancreatic atrophy was detected on abdominal computed tomography. Genetic analysis showed monosomy 7. So the patient was diagnosed as SDS. Pancreatic enzymes and insulin replacement was administered. After clinical and laboratory improvement, she was discharged and she had cyclic neutropenia attacks in her follow up. In the interesting case, because she had neutropenia, findings of malabsorption and pancreatic atrophy, the patient was considered as SDS. Genetic analysis for monosomy 7 confessed the diagnosis. SDS is usually associated with insufficiency of exocrine but not endocrine functions of pancreas. Only a few cases have been reported about diabetes developed in SDS patients before. Coexistence of SDS and diabetes is unlikely to be incidental, the onset and severity of diabetes varies with each patient, and the pathophysiology of developing diabetes remains unclear [3]. Osteoporosis and SDS had been assessed in a few studies in literature. SDS osteoporosis is characterized by reduced numbers of osteoclasts and osteoblasts and low bone turnover and may be directly related to the bone marrow dysfunction and neutropenia. Malabsorption could be an additional risk factor [4]. Rosendahl et al. [5] reported an adult SDS patient with DM and osteoporosis M. Fatih Akdogan Department of Internal Medicine IV, Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey

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.

Evaluation of Glutathione Peroxidase and KCNJ11 Gene Polymorphisms in Patients with New Onset Diabetes Mellitus After Renal Transplantation

Introduction Genetic mutations such as C599T polymorphism in glutathione peroxidase [GPX1] gene and polymorphisms in potassium channel (KCNJ11) genes have recently been proposed in the etiopathogenesis of new onset diabetes mellitus after renal transplantation (NODAT). We aimed to examine the association of GPX1 and KCNJ11 polymorphisms in NODAT. Materials and Methods This is a monocenter case-control study with a total of 118 renal transplant recipients who were divided into 2 groups; NODAT and normal glucose tolerance. Relation of GPX1 and KCNJ11 polymorphisms were investigated between these groups. PCR-RFLP method was used for genotyping of polymorphisms in the GPX1 (rs1050450) and KCNJ11 (rs1805127) genes. Two alleles were visualized for each gene (C/T for GPX1 and A/G for KCNJ11). Results NODAT was correlated with age at transplantation (p<0.001, r=0.380), post-transplant systolic blood pressure (BP) (p=0.02, r=0.211), post-transplant non-HDL cholesterol levels (p=0.01, r=0.803), degree of weight change at the end of the first year (p=0.01, r=0.471), presence of pre-transplant hypertension (HT) (p=0.02, r=0.201), family history of diabetes (p=0.01, r=0.29) and dyslipidemia (p=0.012, r=0.362). GPX1 polymorphism of TT (mutant) allele was significantly more frequent in patients with NODAT (p<0.001, r=0.396) independent from other diabetogenic risk factors. KCNJ11 polymorphisms were similar in both groups and did not show any significant association with NODAT (p=0.10). Conclusions In addition to several diabetogenic risk factors, C599T polymorphisms in GPX1 gene might also contribute to the development of NODAT. Further studies on larger patient series are necessary in order to reach definitive suggestions.

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.

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.