Guideline for screening and diagnosing gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is on the rise, especially with the increase in obesity in childbearing women as well as the rising prevalence of diabetes mellitus type 2. The Maltese gestational women are of no exception especially with an established link to intra-uterine nutritional environment adverse effects as well as to genetic factors. There is no set international screening strategy for GDM and so diagnosis differs between countries. The most common diagnostic test for GDM is by performing a 75g oral glucose tolerance test (oGTT). Most countries and organizations including the World Health Organization have adopted the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria for diagnosing GDM. Performing a 75g OGTT on all women at risk of GDM is expensive as well as unpleasant for the women. A combination of risk criteria including pre-pregnancy body mass index with random plasma glucose and/or fasting plasma glucose based on Maltese and Mediterranean population studies have shown to be a useful screening tool. This tool would help identify women likely to have an abnormal or normal oGTT without the need to perform an oGTT. A screening GDM protocol is essential to pick up and manage at an early stage those that are at risk to develop GDM without the need to have an oGTT performed in every pregnant woman. This would result in better perinatal and maternal outcomes.peer-reviewe

The role of untimed blood glucose in screening for gestational diabetes mellitus in a high prevalent diabetic population

Global prevalence increase of diabetes type 2 and gestational diabetes (GDM) has led to increased awareness and screening of pregnant women for GDM. Ideally screening for GDM should be done by an oral glucose tolerance test (oGTT), which is laborious and time consuming. A randomized glucose test incorporated with anthropomorphic characteristics may be an appropriate cost-effective combined clinical and biochemical screening protocol for clinical practice as well as cutting down on oGTTs. A retrospective observational study was performed on a randomized sample of pregnant women who required an OGTT during their pregnancy. Biochemical and anthropomorphic data along with obstetric outcomes were statistically analyzed. Backward stepwise logistic regression and receiver operating characteristics curves were used to obtain a suitable predictor for GDM without an oGTT and formulate a screening protocol. Significant GDM predictive variables were fasting blood glucose () and random blood glucose (). Different RBG and FBG cutoff points with anthropomorphic characteristics were compared to carbohydrate metabolic status to diagnose GDM without oGTT, leading to a screening protocol. A screening protocol incorporating IADPSG diagnostic criteria, BMI, and different RBG and FBG criteria would help predict GDM among high-risk populations earlier and reduce the need for oGTT test.peer-reviewe

Epidemiology of craniopharyngiomas : a population-based study in Malta

BACKGROUND: Despite being benign tumours, craniopharyngiomas are challenging to manage and can cause significant morbidity and mortality in both the paediatric and adult population. The aim of the study was to analyse the epidemiology of craniopharyngiomas, patient and tumour characteristics through a population-based study in Malta, enabling a better quantification of the disease burden.METHODS: Thorough research was carried out to identify the number of patients who were diagnosed with craniopharyngiomas. Epidemiological data, including both standardised incidence rates (SIR) and prevalence rates, were established in a well-defined population. For incidence estimates, patients who were diagnosed between 2008 and 2019 were included. The background population formed 4.8 million patient-years at risk.RESULT: Twenty-nine subjects were identified and included in our study. The overall SIR was 0.3/100,000/year, with a higher SIR for males compared to females (0.4/100,000/year and 0.2/100,000/year, respectively). The highest SIR was recorded in the 10–19 year age group. The estimated prevalence rate amounted to 5.27/100,000 people, with a lower prevalence rate for childhood-onset when compared to the adult-onset category (2.03/100,000 vs 3.24/100,000 people). The median longest tumour diameter was 31.0 mm (IQR 21–41), with a statistically significant difference between childhood- and adult-onset disease; 43.0 mm (IQR 42.5–47.25) vs 27.0 mm (IQR 20.55–31.55) (P = 0.011).CONCLUSION: Through this population-based study, accurate and up-to-date prevalence and incidence rates for craniopharyngiomas are reported. These provide a clearer reflection of the true health burden of the disease.peer-reviewe

An analysis of craniopharyngioma patients in Malta : epidemiology, patient characterisation and long-term sequelae

BACKGROUND: Despite being benign, craniopharyngiomas are challenging tumours to manage and can cause significant morbidity and mortality in both the paediatric and adult population.METHOD: Our aim was to analyse epidemiology, patient characteristics and long-term sequalae through a population-based study in Malta. A thorough research was carried out to identify patients who were diagnosed with craniopharyngioma in our local population. Subjects were identified from various hospital databases. Presenting features, patient and tumour characteristics, treatment modalities, long-term sequelae and epidemiology were analysed.RESULTS: From a cohort of 29 patients, 62.1% were male. The mean age at presentation was 32.4 years (s.d. ± 19.0). 11 patients (37.9%) were diagnosed with childhood onset craniopharyngioma (age at presentation < 20 years) whilst 18 patients (62.1%) had adult-onset craniopharyngioma. Median follow up period since time of diagnosis was 13.0 years (IQR 5–25). For incidence estimates, 13 patients who were diagnosed between June 2008 and June 2019 were included. The background population formed 4.8 million patient-years at risk. The overall SIR was 3.0/1,000,000/year, with the highest SIR in the 10–19 year age group. The estimated prevalence rate was 52.7/1,000,000 people, with lower prevalence rates for childhood- compared to adult-onset (20.3/1,000,000 vs 32.4/1,000,000 people). Visual disturbances and symptoms secondary to raised intracranial pressure were the commonest presenting complaints. Most tumours were multi-cystic (42.9%) and were commonly located in the intrasellar region with suprasellar extension. The median longest tumour diameter was 31.0 mm (IQR 21–41), with statistically significant difference between childhood- and adult-onset disease; 43.0 mm (IQR 42.5–47.25) vs 27.0 mm (IQR 20.55–31.55) (P = 0.011). All 24 patients who underwent neurosurgical intervention (82.8%) had adamantinomatous craniopharyngioma. 58.6% of patients required radiotherapy. The commonest long-term sequalae were hormone deficiencies (93.1%), followed by obesity (20.7%). Most patients required hormonal supplementation of more than one pituitary axis. 7 patients (30.4%) had evidence of tumour regrowth or recurrence during follow-up. 3 patients passed away throughout their follow up.CONCLUSION: From a cohort of 29 patients, 62.1% were male. The mean age at presentation was 32.4 years (s.d. ± 19.0). 11 patients (37.9%) were diagnosed with childhood onset craniopharyngioma (age at presentation < 20 years) whilst 18 patients (62.1%) had adult-onset craniopharyngioma. Median follow up period since time of diagnosis was 13.0 years (IQR 5–25). For incidence estimates, 13 patients who were diagnosed between June 2008 and June 2019 were included. The background population formed 4.8 million patient-years at risk. The overall SIR was 3.0/1,000,000/year, with the highest SIR in the 10–19 year age group. The estimated prevalence rate was 52.7/1,000,000 people, with lower prevalence rates for childhood- compared to adult-onset (20.3/1,000,000 vs 32.4/1,000,000 people). Visual disturbances and symptoms secondary to raised intracranial pressure were the commonest presenting complaints. Most tumours were multi-cystic (42.9%) and were commonly located in the intrasellar region with suprasellar extension. The median longest tumour diameter was 31.0 mm (IQR 21–41), with statistically significant difference between childhood- and adult-onset disease; 43.0 mm (IQR 42.5–47.25) vs 27.0 mm (IQR 20.55–31.55) (P = 0.011). All 24 patients who underwent neurosurgical intervention (82.8%) had adamantinomatous craniopharyngioma. 58.6% of patients required radiotherapy. The commonest long-term sequalae were hormone deficiencies (93.1%), followed by obesity (20.7%). Most patients required hormonal supplementation of more than one pituitary axis. 7 patients (30.4%) had evidence of tumour regrowth or recurrence during follow-up. 3 patients passed away throughout their follow up.peer-reviewe

Radiological and functional analysis of a cohort of adrenal adenomas

AIM: A cohort of adrenal incidentalomas which had radiological or histological characteristics in keeping with an adrenal adenoma was analysed in terms of the radiological and functional characteristics.METHODS: A retrospective cross-sectional analysis of a cohort of adrenal adenomas was carried out. Lesions were followed up for a median of 8.2months (IQR 1.4–34.6). In the majority of patients (69.95%), the diagnosis of a benign adrenal adenoma was made via an unenhanced CT scan (density of lesion 10HU on an unenhanced CT scan) or had a contrast scan in the first instance, the absolute or relative washouts were calculated in 11.0% and 13.5% respectively. MRI was the imaging modality of choice in 1 patient. 3 patients had an adrenalectomy, with histology confirming an adrenocortical adenoma.RESULTS: 209 patients with adrenal adenomas were included. Out of the whole cohort, 111 patients were females (53.1%). The mean age of patients at diagnosis was 62.3 years (± 12.1SD). Left sided lesions were noted to be the commoner lesions, being present in 61.2% and bilateral lesions in 6.2%. The median longest radiological diameter (on CT or MRI) was 19.0 mm (IQR15.0–25.0). During this follow up period, practically no change in size of the adenomas was identified (median change in size 0 mm (IQR 0–1). Morning cortisol following 1mg overnight dexamethasone suppression was >50 nmol/l in 34.2% in keeping with possible autonomous cortisol secretion. 4 out of these patients had cortisol above 138nmol/l in keeping with autonomous cortisol secretion. 0900 h cortisol post ODST correlated positively with age (P = 0.003) and longest radiological diameter of adenoma (P < 0.001) and negatively with DHEAS (P < 0.001). Multiple logistic regression analysis maintained the positive correlation between 9am post ODST cortisol with age (OR 1.066 P = 0.004) and longest radiological tumour diameter (OR 1.168 P < 0.001). A high aldosterone renin ratio was found in 36% of patients. Out of these patients, 22% also had a level of cortisol following overnight dexamethasone suppression of more than 50 nmol/l.CONCLUSION: Interesting correlations between biochemical and radiological parameters in patients with adrenal adenomas have been established. The correlation between 0900 h cortisol following the overnight dexamethasone suppression test and age is not documented in the literature.peer-reviewe

Ipilumumab induced hypophysitis

INTRODUCTION: Immunotherapy has advanced significantly over the past years. Immune-related adverse events (IRAEs) are various and include endocrinological complications such as Ipilimumab-induced hypophysitis (IIH). The incidence of this cytotoxic T-lymphocyte antigen 4 antibody ranges from 0 to 17%. Patients usually present with symptoms secondary to hormonal insufficiencies.CASE REPORT: A 73 year-old lady, known case of metastatic melanoma on immunotherapy presented with a 1 week history of pre-syncopal episodes and nausea. She gave a few week history of non-vertiginous dizziness, lethargy and headache. The patient had received her third course of ipilimumab few days prior to presentation. Cortisol level during admission was 23 nmol/l, from a previously normal level of 993 nmol/l few weeks prior. The patient had low T4 and TSH levels (0.080 mIU/ml and 6.7 pmol/l respectively) together with low FSH (2.4 U/l), LH (0.6 U/l) and prolactin levels (59 mIU/l) in keeping with panhypopituitarism. The patient was started on glucocorticoids and thyroxine with rapid improvement of her symptoms.IMAGING: MRI brain at presentation showed a 1.5×1.4×1.2 cm sellar lesion involving the pituitary gland with mild suprasellar extension. The lesion demonstrated low T1 and mildly hyperintense T2 signal intensity and enhanced avidly following contrast administration, with a central non-enhancing component. The infundibulum was thickened. Repeat MRI after 3 months revealed complete resolution of the sellar and infundibular changes with normalization of the gland confirming the initial hypothesis of hypophysitis.DISCUSSION: Literature suggests that a high index of suspicion for hypophysitis needs to be kept in mind in patients receiving immunotherapy. It is advised that patients undergo 6 monthly assessment of pituitary function and MR scans should be compared to previous imaging if available to assess for a change in pituitary size. In hypophysitis, the degree of pituitary enlargement should reduce after treatment as was in our case. If this is not observed, alternative diagnoses such as pituitary metastasis should be considered. It is debatable whether patients with IIH should be administered higher dosages of glucocorticoids in contrast to physiological replacement, since there are concerns that treatment with high dosages of glucocorticoids may affect the antitumor efficacy of Ipilimumab. In our patient, a physiological replacement dose was sufficient for her to improve clinically and have complete resolution of symptoms after 3 months.CONCLUSION: Development of IIH can precipitate acute adrenal failure or crisis. Early diagnosis and management are vital to prevent complications including increased morbidity and mortality rates.peer-reviewe

When a rare syndrome keeps behaving in rarer manners over and over again!

Pituitary apoplexy arises when haemorrhage and/or infarction occurs within a pituitary tumour. In Malta, the estimated standardised incidence rate (SIR) of apoplexy is 0.15/100,000/yr. ACTH secreting pituitary adenomas have a SIR of 0.17/100,000/year.CASE REPORT: A 46 year-old gentleman with a history of poorly controlled diabetes mellitus was referred following the diagnosis of a pituitary adenoma. He had presented with a 1.5 year history of left third cranial neuropathy with complete ptosis. Magnetic resonance imaging (MRI) showed a 3.2×1.5 cm lesion extending into the suprasellar cistern, abutting the optic chiasm and extending into the cavernous sinuses, more pronounced on the left side. Biochemical assessment revealed cortisol of 483 nmol/l, prolactin 31 mIU/l, Testosterone 3.5 nmol/l, LH 1.9 U/l, FSH 4.5 U/l, TSH 2.34 micIU/l and T4 12.27 pmol/l. The patient had an inadequately suppressed cortisol level (149 mmol/l) on a 48-hour low dose dexamethasone suppression test and a high ACTH (102 pg/ml) in keeping with ACTH-dependent Cushing’s syndrome. The patient was referred for infra-petrosal sinus sampling, which confirmed an ACTH secreting pituitary macroadenoma. The patient could not undergo surgery at the time in view of an infected diabetic foot ulcer. He was initiated on Metyrapone in an effort to control his hypercortisolaemia. The patient presented two months later with severe headache and new onset visual disturbances. He developed a right III and VI cranial nerve (CN) palsies. Ophthalmological assessment revealed a reduction in visual acuity. Areas of hyperintensity in the pituitary adenoma were noted on unenhanced T1 MRI scan and there was lack of enhancement on a contrast scan, in keeping with apoplexy. Urgent debulking was carried out through a trans-sphenoidal approach. Clinical symptoms and visual disturbances showed improvement post-operatively; the right 3rd and 6th CN palsies improved but he had a persistent right temporal visual field defect. Histology confirmed pituitary apoplexy due to tumour infarction of a functional (ACTH secreting) pituitary macroadenoma.CONCLUSION: Presentation of Cushing’s Disease can be very varied and the work up is extensive and elaborate with a number of different steps. Cushing’s syndrome is associated with multiple comorbidities including increased risk of cardiovascular events, neurological consequences osteoporosis and poor quality of life. Hence, it is imperative that an early diagnosis is made as early as possible so that the condition is appropriately treated. Although apoplexy is rare, this complication needs to be kept in mind as an inherent risk when managing patients with pituitary adenomas.peer-reviewe

Gender and age-matched case control study of a cohort of adrenal adenomas

Background: The majority of adrenal incidentalomas are benign and patients can be reassured, but a personalized and multidisciplinary approach is required when dealing with these lesions, since they might be linked with various comorbidities. The aim of our study was to carry out an in-depth analysis of the biochemical workup of adrenal incidentalomas and comparing the results with controls. Methods: 252 patients with an incidentally discovered adrenal adenoma were identified. A retrospective cross-sectional analysis of this cohort was carried out. A corresponding cohort of 252 gender and aged-matched patients (+/- 5 years) who underwent a CT scan for a similar indication and on the same day as the cases was recruited. A comparison of numerous parameters was carried out.peer-reviewe

An analysis of hypocalcaemia post thyroidectomy : diagnosis and predictors

BACKGROUND: Post-thyroidectomy hypocalcaemia is a common complication with significant short and long term complications. The aim of this study was to determine the incidence and predictors of post-thyroidectomy hypocalcaemia (corrected calcium <2.1mmol/l).METHOD: A total of 183patients who underwent total thyroidectomy between 2012 and 2015 in a national general hospital were included in this retrospective study. Clinical and biochemical data were obtained from electronic and hard copy medical records.RESULTS: Out of a total of 183 patients, 142 (77.6%) were female, while 41 were males (22.4%). Ages ranged from 15 to 84 years, with a mean of 50.6 years (SD 15.84 years). There was variation in the incidence of hypocalcemia dependent on the timing of measurement of calcium on post-op day 1 (POD1) and the measuring of calcium on subsequent days. The incidence of post-operative hypocalcaemia on day 1 was 17.5% (n=32). The indications for surgery included Graves’ disease (62 patients, 33.88%), multi-nodular goitre (50 patients, 27.32%), malignancy (28 patients, 16.39%), the presence of a thyroid nodule (22 patients, 12.02%), hyperparathyroidism (18 patients, 9.83%) and in 3 patients (1.63%)the indication was unclear. A lower preoperative uncorrected calcium was associated with post-thyroidectomy hypocalcaemia (P=0.048). However it was found that the incidence of post-thyroidectomy hypocalcaemia was underestimated by 55.5% if only POD1 measurement was used.DISCUSSION: Measuring calcium on POD1 may miss patients who would subsequently develop hypocalcaemia. Other possible contributing factors for post-op hypocalcaemia, including age, gender, histology and indication for surgery were not found to be statistically significant, and could not be used to predict who will develop hypocalcaemia. This emphasises the need for stringent guidelines for assessing and managing patients undergoing total thyroidectomy and possible associated hypocalcaemia.peer-reviewe

An analysis of blood parameter changes in Cushing's syndrome - a population-based study

Aim: Glucocorticoids play a significant role in inflammation and immune system disruption. Our study aimed to analyse different biochemical and blood count indices and serum inflammationbased scores in patients with all different causes of endogenous Cushing’s Syndrome (CS) in a welldefined population.Methods: Clinical records of 35 patients diagnosed with CS between 2008 and 2020 at the only central national health service hospital in Malta, were retrospectively analysed. Detailed clinical and biochemical data were obtained for each patient. Correlation and receiver operator characteristics (ROC) curve analyses were used to establish a threshold value for different variables to predict malignant CS.peer-reviewe