Landscape of congenital adrenal hyperplasia cases in adult endocrinology clinics of Türkiye-a nation-wide multicentre study.

BACKGROUND AND AIMS: Congenital adrenal hyperplasia (CAH) is a group of disorders that affect the production of steroids in the adrenal gland and are inherited in an autosomal recessive pattern. The clinical and biochemical manifestations of the disorder are diverse, ranging from varying degrees of anomalies of the external genitalia to life-threatening adrenal insufficiency. This multicenter study aimed to determine the demographics, biochemical, clinical, and genetic characteristics besides the current status of adult patients with CAH nationwide. METHODS: The medical records of 223 patients with all forms of CAH were evaluated in the study, which included 19 adult endocrinology clinics. A form inquiring about demographical, etiological, and genetic (where available) data of all forms of CAH patients was filled out and returned by the centers. RESULTS: Among 223 cases 181 (81.16%) patients had 21-hydroxylase deficiency (21OHD), 27 (12.10%) had 11-beta-hydroxylase deficiency (110HD), 13 (5.82%) had 17-hydroxylase deficiency (17OHD) and 2 (0.89%) had 3-beta-hydroxysteroid-dehydrogenase deficiency. 21OHD was the most prevalent CAH form in our national series. There were 102 (56.4%) classical and 79 (43.6%) non-classical 210HD cases in our cohort. The age of the patients was 24.9 ± 6.1 (minimum-maximum: 17-44) for classical CAH patients and 30.2 ± 11.2 (minimum-maximum: 17-67). More patients in the nonclassical CAH group were married and had children. Reconstructive genital surgery was performed in 54 (78.3%) of classical CAH females and 42 (77.8%) of them had no children. Thirty-two (50.8%) NCAH cases had homogenous and 31 (49.2%) had heterogeneous CYP21A2 gene mutations. V281L pathological variation was the most prevalent mutation, it was detected in 35 (55.6%) of 21OHD NCAH patients. CONCLUSION: Our findings are compatible with the current literature except for the higher frequency of 110HD and 17OHD, which may be attributed to unidentified genetic causes. A new classification for CAH cases rather than classical and non-classical may be helpful as the disease exhibits a large clinical and biochemical continuum. Affected cases should be informed of the possible complications they may face. The study concludes that a better understanding of the clinical characteristics of patients with CAH can improve the management of the disorder in daily practice.

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.

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.

Prevalence of papillary thyroid cancer in subacute thyroiditis patients may be higher than it is presumed: retrospective analysis of 137 patients.

Background The association of subacute thyroiditis (SAT) and papillary thyroid carcinoma is a rare finding. In this study, we aimed to investigate the prevalence of differentiated thyroid cancer in a cohort of patients followed with the diagnosis of SAT. Patients and methods We retrospectively screened medical records of Endocrinology and Metabolism outpatient clinic in the past 20 years for patients with SAT. Patients with nodules and suspicious ultrasonography findings who underwent fine needle aspiration biopsy (FNAB) and operated due to malignancy risk were identified. Results We identified 137 (100 females, 37 males) patients with reliable records to confirm the diagnosis of SAT. The mean age of female patients was 41.1 ± 9.1 (range, 20-64) and of male patients was 43.0 ± 9.3 (range, 20-65). One or more FNAB was performed in 23 of the patients (16.8%) at the beginning and/or during the follow-up period when needed. Seven patients with suspicious FNAB findings were operated, and histopathological examination of the nodules confirmed the diagnosis of papillary thyroid carcinoma in 6 patients (4.4%). Conclusions Our observations suggesting a relatively higher prevalence of thyroid cancer in a small series of SAT patients warrant further studies to identify the real frequency of differentiated thyroid cancer and its association with inflammatory pathogenesis of SAT. This finding is compatible with the trend of increased thyroid cancer incidence all over the world. A repeat ultrasonography after resolution of clinical and inflammatory findings, and FNAB should be recommended to all patients with suspicious nodules.

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 (Hashimoto's 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.

Withdrawal of dopamine agonist therapy in prolactinomas: In which patients and when?

PURPOSE: The aim of the study was to assess the effect of dopamine agonist (DA) withdrawal, the current recurrence rate of hyperprolactinemia, and possible factors that predict recurrence in patients with prolactinoma. METHODS: We evaluated DA withdrawal in 67 patients with prolactinoma (50 female/17 male) who received DA treatment for at least 2 years and showed normalization of prolactin (PRL) levels and tumor disappearance or ≥50 % tumor shrinkage, retrospectively. Accordingly, patients were divided into two groups as remission and recurrence groups, and factors that predict recurrence were evaluated. RESULTS: The overall remission rate was 46 %; the remission ratios were 65 % in microprolactinomas and 36 % in macroprolactinomas. Remission rates were 39 % in the bromocriptine withdrawal group and 55 % in the cabergoline withdrawal group. The maximum tumor diameter and baseline PRL levels were significantly higher in the recurrence group (p = 0.001 and p = 0.003, respectively). The mean duration of DA therapy was significantly longer in the remission group (88.7 ± 48.1 and 66.7 ± 30.4 months, respectively, p = 0.026).The mean time to recurrence was 5.3 ± 3.2 months. The mean PRL levels at recurrence time were significantly lower than baseline PRL levels (p = 0.001). CONCLUSION: The most important predictors of recurrence were maximum tumor diameter and baseline PRL levels in this study. The remission rate in our study group was higher, which was thought to be associated with the longer duration of DA treatment and that our patients were selected according to certain criteria. Despite these positive results, close monitoring is necessary for detection of early and late recurrence, especially within the first year after DA withdrawal.