Impulse control disorders in patients with dopamine agonist-treated pituitary adenomas: a cross-sectional multicenter study.

BACKGROUND: Impulse control disorders (ICDs) have been described as underrecognized side effects of dopamine agonists (DAs) in neurological disorders but are not sufficiently understood in endocrine conditions. OBJECTIVE: To identify the prevalence of DAs induced ICDs and determine potential risk factors related to these disorders in patients with prolactinoma and non-function pituitary adenomas (NFPAs). METHODS: This is a cross-sectional multicenter study involving 200 patients with prolactinoma and NFPAs, who received follow-ups in tertiary referral centers. DA-induced ICDs were assessed using ICD questionnaires modified from prior studies. RESULT: At least one ICD was reported by 52% of participants, among whom 28.5% mentioned compulsive shopping, 24.5% punding, and 24.5% hypersexuality. Furthermore, 33% of the patients reported the presence of one type of ICD behavior, while 12% specified two and 7% had three types of such behavior. The multivariable logistic regression showed that the significant risk factors of ICD were younger age (adjusted odds ratio [AOR]: 0.92, 95% confidence interval [CI]: 0.88-0.97, p 0.001), being single (AOR: 0.15, 95%CI: 0.03-0.84, p 0.03), and a positive history of psychiatric illness (AOR: 7.67, 95% CI: 1.37-42.97, p 0.021). CONCLUSION: ICDs with a broad range of psychiatric symptoms are common in individuals with DA-treated prolactinoma and NFPAs. Endocrinologists should be aware of this potential side effect, particularly in patients with a personal history of psychiatric disorder.

Characteristics and Management of Papillary Thyroid Microcarcinoma in the United Arab Emirates: Experience from a Large Tertiary Hospital.

Background: Recent guidelines in the management of papillary thyroid microcarcinoma (PTMC) recommend limiting surgery. However, trends in the characteristics and management of PTMC from the Middle East and North Africa region is lacking. Objectives: To determine the clinical features, management strategy, and outcomes of PTMC in a large tertiary care center in the United Arab Emirates (UAE). Patients and Methods: This retrospective study included all patients diagnosed with PTMC (i.e., size ≤10 mm) at Tawam Hospital, Al Ain, UAE, between 2008 and 2019. Tumor histopathology, management strategy, and outcomes were the primary analyzed variables. Results: A total of 213 patients with PTMC met the inclusion criteria, of which 83.6% were women and 58.7% were Emiratis. The majority had the classical tumor subtype (76.1%) and tumor of size 5-10 mm (71.4%). Multifocal disease was present in 41.1% and lymph node metastasis (LNM) in 16.6% of the patients. According to the 2015 American Thyroid Association categorization, the majority (93.9%) had a low-risk disease, and all except one patient had Stage 1 disease. Total thyroidectomy was performed in 91.1% of the patients, and 47.9% received radioiodine (RAI) therapy. None of the patients were under active surveillance strategy. RAI treatment was used more often in patients with non-incidental tumors, larger tumor size, multifocal disease, positive LNM, tumors in the intermediate/high ATA category, and those who underwent total thyroidectomy or neck dissection (for all, P < 0.05). After a median follow-up of 32.4 months, about 73% had an excellent response to dynamic risk stratification assessment, and only one patient had disease recurrence. Conclusions: The majority of the patients had low-risk PTMC, yet most patients underwent total thyroidectomy, and almost 50% were treated with RAI ablation. Further studies are needed to determine if these trends are also present regionally and to explore reasons for not adopting a less aggressive approach in this indolent tumor.

Continuous subcutaneous insulin infusion is associated with a better glycemic control than multiple daily insulin injections without difference in diabetic ketoacidosis and hypoglycemia admissions among Emiratis with Type 1 diabetes.

AIMS: To characterizes Emiratis patients with Type 1 diabetes (T1D) and compares outcomes between continuous subcutaneous insulin infusion (CSII) versus multiple daily insulin injections (MDI) users. The WHO-Five Well-Being Index (WHO-5) score was used to screen for depression. METHODS: In this cross-sectional study; sociodemographic, clinical characteristics and insulin replacement regimens were collected on patients with T1D between 2015-2018. RESULTS: 134 patients with mean age of 20.9±7.5 years were included. Females constitute 56.7% and 50.7% had diabetes duration of >10 years. Diabetic ketoacidosis (DKA) at presentation was reported in 46.3%. Average glycemic control over preceding 12months was satisfactory (less than 7.5%), suboptimal (7.5-9%), and poor (more than 9%) in 26.6%, 42.7% & 30.6% of the patients, respectively. Higher proportion of patients using CSII achieved satisfactory or suboptimal glycemic control compared to patients with MDI (P = 0.003). The latest median /IQR HbA1c was significantly lower (P = 0.041) in patients using CSII (8.2 /1.93%) compared to MDI (8.5/2.45%). There was no significant difference between two groups in DKA, severe hypoglycemia or total WHO-5 score. CONCLUSIONS: CSII usage was associated with better glycemic control than MDI, although no difference in DKA and severe hypoglycemia. The overall glycemic control among Emiratis subjects with T1D is unsatisfactory and needs more rigorous patient counseling and education.

Decline in radioiodine use but not total thyroidectomy in thyroid cancer patients treated in the United Arab Emirates - A retrospective study.

OBJECTIVES: To assess the trend of clinicopathological features and treatment modalities in patients with thyroid cancer (TC) in the largest oncology center in the United Arab Emirates (UAE). METHODS: A retrospective analysis of patients with TC presenting to a tertiary care hospital in Al Ain, UAE between September 2008 and December 2018 identified using ICD 9 & 10 codes was performed. Data on demographics, histopathology, surgical extent, and use of Radioiodine (RAI) were extracted. Exact logistic and ordinal logistic regressions were performed to analyze the annual trend in features and management of TC, and logistic regression analysis was performed to identify predictors of total thyroidectomy and RAI use. RESULTS: A total of 762 patients were included in the analysis (mean age: 39.6 ± 12.6 years, 45 (60%) women). The majority (92.2%) were diagnosed with papillary thyroid cancer (PTC) and 83.9% had tumor size of <4 cm. All patients underwent surgery (93.8% total thyroidectomy, 6.2% lobectomy) and 77.4% received RAI therapy overall with a significant (p < 0.001) decline from 100% in 2008 to 60% in 2018. In multivariate analysis, nationality, and lymph node (LN) involvement were significant predictors of total thyroidectomy, while nationality, LNs, year of diagnosis, and tumor size significantly predicted RAI use. CONCLUSION: Most patients in our cohort were diagnosed with localized PTC with no significant change in the extent of surgical approach but a substantial decline in RAI therapy administration over time. Nationality and LN involvement were significant predictors of surgical extent and RAI use.

Management of Diabetes Insipidus following Surgery for Pituitary and Suprasellar Tumours.

Central diabetes insipidus (CDI) is a common complication after pituitary surgery. However, it is most frequently transient. It is defined by the excretion of an abnormally large volume of dilute urine with increasing serum osmolality. The reported incidence of CDI after pituitary surgery ranges from 0-90%. Large tumour size, gross total resection and intraoperative cerebrospinal fluid leak usually pose an increased risk of CDI as observed with craniopharyngioma and Rathke's cleft cysts. CDI can be associated with high morbidity and mortality if not promptly recognised and treated on time. It is also essential to rule out other causes of postoperative polyuria to avoid unnecessary pharmacotherapy and iatrogenic hyponatremia. Once the diagnosis of CDI is established, close monitoring is required to evaluate the response to treatment and to determine whether the CDI is transient or permanent. This review outlines the evaluation and management of patients with CDI following pituitary and suprasellar tumour surgery to help recognise the diagnosis, consider the differential diagnosis, initiate therapeutic interventions and guide monitoring and long-term management.

Ultrasound-guided fine needle aspiration cytology and ultrasound examination of thyroid nodules in the UAE: A comparison.

BACKGROUND: Thyroid nodules are a common clinical finding and most are benign, however, 5-15% can be malignant. There is limited regional data describing the accuracy of ultrasound-guided fine needle aspiration (FNA) cytological examination compared to ultrasound examination of thyroid in patients who have undergone thyroid surgery. METHODS: A retrospective analysis of ultrasonographic (US) reports, FNA cytology reports and histopathology reports of 161 thyroid nodules presented at the endocrine center at Tawam hospital in Al Ain city, the United Arab Emirates during the period 2011-2019 was performed. US reports and images with FNA cytopathology reports and slides were reviewed by an independent radiologist and pathologist. RESULTS: In total, 40 nodules were reported as benign by US examination, while very low suspicious, low suspicious, intermediate suspicious and highly suspicious categories were reported in 21, 41, 14 and 45 nodules respectively. In addition, 68 nodules were reported as benign (Bethesda category II), while atypical follicular cells of unknown significance (Bethesda category III), follicular neoplasm (Bethesda category IV), suspicious for malignancy (Bethesda category V), and malignant (Bethesda category VI) categories were reported in 33, 9, 24 and 27 nodules respectively. The risk of malignancy for US benign nodules was 5%, while the risks of malignancy in very low suspicious, low suspicious, intermediate suspicious and highly suspicious nodules were 52%, 36%, 100% and 87%, respectively. The risk of malignancy for Bethesda category II was 3%, while the risks of malignancy in category III, IV, V and VI were 58%, 67%, 96% and 100%, respectively. CONCLUSION: Thyroid FNA cytological examination and ultrasonography are key tools in predicting malignancy in thyroid nodules. Thyroid nodules with the diagnosis of Bethesda category III & IV run a high risk of malignancy thus more vigilance is required.

Contemporary Management of Clinically Non-functioning Pituitary Adenomas: A Clinical Review.

Non-functioning pituitary adenomas (NFPAs) are benign pituitary tumours that constitute about one-third of all pituitary adenomas. They typically present with symptoms of mass effects resulting in hypopituitarism, visual symptoms, or headache. Most NFPAs are macroadenomas (>1 cm in diameter) at diagnosis that can occasionally grow quite large and invade the cavernous sinus causing acute nerve compression and some patients may develop acute haemorrhage due to pituitary apoplexy. The progression from benign to malignant pituitary tumours is not fully understood; however, genetic and epigenetic abnormalities may be involved. Non-functioning pituitary carcinoma is extremely rare accounting for only 0.1% to 0.5 % of all pituitary tumours and presents with cerebrospinal, meningeal, or distant metastasis along with the absence of features of hormonal hypersecretion. Pituitary surgery through trans-sphenoidal approach has been the treatment of choice for symptomatic NFPAs; however, total resection of large macroadenomas is not always possible. Recurrence of tumours is frequent and occurs in 51.5% during 10 years of follow-up and negatively affects the overall prognosis. Adjuvant radiotherapy can decrease and prevent tumour growth but at the cost of significant side effects. The presence of somatostatin receptor types 2 and 3 (SSTR3 and SSTR2) and D2-specific dopaminergic receptors (D2R) within NFPAs has opened a new perspective of medical treatment for such tumours. The effect of dopamine agonist from pooled results on patients with NFPAs has emerged as a very promising treatment modality as it has resulted in reduction of tumour size in 30% of patients and stabilization of the disease in about 58%. Despite the lack of long-term studies on the mortality, the available limited evidence indicates that patients with NFPA have higher standardized mortality ratios (SMR) than the general population, with women particularly having higher SMR than men. Older age at diagnosis and higher doses of glucocorticoid replacement therapy are the only known predictors for increased mortality.

Prevalence and characteristics of sellar masses in the city of Al Ain, United Arab Emirates: 2010 to 2016.

BACKGROUND: The prevalence of sellar masses (SMs) is reported in Europe and North America but only limited data are available from the Middle East and North Africa (MENA) region. OBJECTIVES: Assess the prevalence and characteristics of SMs in Al Ain city, United Arab Emirates. DESIGN: Retrospective, descriptive multicenter study. SETTING: Three endocrine centers in Al Ain. PATIENTS AND METHODS: All patients diagnosed with SMs in the city of Al Ain, Emirate of Abu Dhabi, between 2011 and 2016 were evaluated. Cases were identified using ICD 9 and 10 codes and demographic and clinical data were collected. The prevalence rate was calculated for patients alive and residing in Al Ain city until 31 December 2016. MAIN OUTCOME MEASURES: Clinical presentations and prevalence rate. SAMPLE SIZE: 272. RESULTS: The mean (SD) age on presentation was 40.8 (14.3) years (range: 6-114 years, median: 40.0). The 170 (61.8%) females and 128 (46.5%) were native citizens of the United Arab Emirates. Two hundred and forty five (90%) patients had pituitary adenomas (PAs) while 27 (10%) had non-pituitary sellar lesions. The four most common SMs were prolactinoma (n=139, 51.1%), nonfunctioning adenoma (NFA) (n= 69, 25.4%), somatotroph adenoma (n=32, 11.8%) and craniopharyngioma (n=15, 5.5%). Patients with prolactinoma, corticotroph adenoma, and Rathke's cleft cyst had small sellar masses (<1 centimeter) while the majority of patients with other SMs had macroadenomas. Hypogonadism and growth hormone deficiency was present in 41.8% and 20.5% of the patients, respectively. Of 268 patients with available data, 82 patients underwent surgery while 25 patients received radiotherapy. At the end of 2016, 197 patients were residing in Al Ain city. The overall prevalence of SMs was 25.7/100 000 with PAs constituting most of these masses (n=177) for a prevalence of 23.1/100 000. CONCLUSIONS: This is the first study of SMs in the United Arab Emirates and the MENA region. Prolactinoma and NFA were the two most common SMs. Further studies are needed to explore the reasons for the lower prevalence of SMs in our region compared with other countries. LIMITATIONS: Retrospective design, relatively small sample size. CONFLICT OF INTEREST: None.

Aetiologies of Hyperprolactinaemia: A retrospective analysis from a tertiary healthcare centre.

OBJECTIVES: This study aimed to evaluate the aetiologies of hyperprolactinaemia in the United Arab Emirates (UAE). METHODS: This retrospective study used laboratory databases to identify all patients who underwent evaluation for prolactin at Tawam Hospital, Al Ain, UAE, between 2009 and 2015. Of those 2,280 patients, all patients with low or normal prolactin (n = 1,315) were excluded. Subsequently, charts of the remaining patients (n = 965) with hyperprolactinaemia were reviewed and those with incomplete work-ups or insufficient documentation of the hyperprolactinaemia's aetiology were excluded (n = 458). RESULTS: A total of 507 patients were included in the study. The average age at prolactin evaluation was 36 ± 13.2 years and the majority (67.1%) of patients were female. The most common reasons for requesting prolactin were menstrual disorders (29.5%), infertility (18%), evaluation of sellar masses (14.3%), ruling out seizures (13.4 %) and monitoring while on psychiatric medications (8.7%). The most common causes of hyperprolactinaemia were prolactinoma (17%), transient hyperprolactinaemia (14.6%), drug-induced side effects (14.4%), polycystic ovarian syndrome (11.8%) and seizure disorder (7.7%). In females, common aetiologies were prolactinomas, transient and idiopathic hyperprolactinaemia, while sellar masses, seizures, chronic kidney disease and acute illnesses were common aetiologies of hyperprolactinaemia in males. The prolactin level varied between the different aetiologies and a level of >250 ng/mL was suggestive of macro-prolactinoma. CONCLUSION: A significant proportion of patients with hyperprolactinaemia have transient hyperprolactinaemia. Before further investigations are carried out, prolactin level assessment should be repeated, especially in patients with mild hyperprolactinaemia.

Unusual AIP mutation and phenocopy in the family of a young patient with acromegalic gigantism.

Early-onset acromegaly causing gigantism is often associated with aryl-hydrocarbon-interacting receptor protein (AIP) mutation, especially if there is a positive family history. A15y male presented with tiredness and visual problems. He was 201 cm tall with a span of 217 cm. He had typical facial features of acromegaly, elevated IGF-1, secondary hypogonadism and a large macroadenoma. His paternal aunt had a history of acromegaly presenting at the age of 35 years. Following transsphenoidal surgery, his IGF-1 normalized and clinical symptoms improved. He was found to have a novel AIP mutation destroying the stop codon c.991T>C; p.*331R. Unexpectedly, his father and paternal aunt were negative for this mutation while his mother and older sister were unaffected carriers, suggesting that his aunt represents a phenocopy. LEARNING POINTS: Typical presentation for a patient with AIP mutation with excess growth and eunuchoid proportions.Unusual, previously not described AIP variant with loss of the stop codon.Phenocopy may occur in families with a disease-causing germline mutation.

A comparative, population-based analysis of pituitary incidentalomas vs clinically manifesting sellar masses.

PURPOSE: Sellar masses may present either with clinical manifestations of mass effect/hormonal dysfunction (CMSM) or incidentally on imaging (pituitary incidentaloma (PI)). This novel population-based study compares these two entities. METHODS: Retrospective analysis of all patients within a provincial pituitary registry between January 2006 and June 2014. RESULTS: Nine hundred and three patients were included (681 CMSM, 222 PI). CMSM mainly presented with secondary hormone deficiencies (SHDs) or stalk compression (29.7%), whereas PIs were found in association with neurological complaints (34.2%) (P < 0.0001). PIs were more likely to be macroadenomas (70.7 vs 49.9%; P < 0.0001). The commonest pathologies among CMSM were prolactinomas (39.8%) and non-functioning adenomas (NFAs) (50%) in PI (P < 0.0001). SHDs were present in 41.3% CMSM and 31.1% PI patients (P < 0.0001) and visual field deficit in 24.2 and 29.3%, respectively (P = 0.16). CMSM were more likely to require surgery (62.9%) than PI (35.8%) (P < 0.0005). The commonest surgical indications were impaired vision and radiological evidence of optic nerve compression. Over a follow-up period of 5.7 years for CMSM and 5.0 years for PI, tumour growth/recurrence occurred in 7.8% of surgically treated CMSM and 2.6% without surgery and PI, 0 and 4.9%, respectively (P = 1.0). There were no significant differences in the risk of new-onset SHD in CMSM vs PI in those who underwent surgery (P = 0.7) and those who were followed without surgery (P = 0.58). CONCLUSIONS: This novel study compares the long-term trends of PI with CMSM, highlighting the need for comprehensive baseline and long-term radiological and hormonal evaluations in both entities.

Analysis and natural history of pituitary incidentalomas.

OBJECTIVES: Pituitary incidentalomas (PI) are frequently found on brain imaging. Despite their high prevalence, little is known about their long-term natural history and there are limited guidelines on how to monitor them. METHODS: We conducted a retrospective study to compare epidemiological characteristics at presentation and the natural history of PI in population-based vs referral-based registries from two tertiary-care referral centers in Canada. RESULTS: A total of 328 patients with PI were included, of whom 73% had pituitary adenomas (PA) and 27% had non-pituitary sellar masses. The commonest indications for imaging were headache (28%), dizziness (12%) and stroke/transient ischemic attack (TIA) (9%). There was a slight female preponderance (52%) with a median age of 55 years at diagnosis; 71% presented as macroadenomas (>10mm). Of PA, 25% were functioning tumors and at presentation 36% of patients had evidence of secondary hormonal deficiency (SHD). Of the total cohort, 68% were treated medically or conservatively whereas 32% required surgery. Most tumors (87% in non-surgery and 68% in post-surgery group) remained stable during follow-up. Similarly, 84% of patients in the non-surgery and 73% in the surgery group did not develop additional SHD during follow-up. The diagnosis of non-functioning adenoma was a risk factor for tumor enlargement and a change in SHD status was associated with a change in tumor size. CONCLUSIONS: Our data suggest that most PI seen in tertiary-care referral centers present as macroadenomas and may frequently be functional, often requiring medical or surgical intervention.