Hyponatraemia : is it clinically relevant?

Hyponatraemia, defined as a sodium concentration <135mmol/l, is the most common electrolyte imbalance encountered in clinical practice. Symptoms can range from seemingly asymptomatic to severe and even life-threatening. Hyponatraemia is usually managed by clinicians from various fields, leading to a wide variety of approaches to its diagnosis and treatment.peer-reviewe

Lipodystrophy : focus on HIV Lipodystrophy

Lipodystrophy is a rare condition which can be inherited or acquired, localised or generalised. It is characterised by abnormal adipose tissue distribution and in some cases underlying metabolic derangement, including diabetes mellitus, hypertriglyceridemia, hepatic steatosis, polycystic ovaries and acanthosis nigricans. Today, most cases of lipodystrophy are associated with human immunodeficiency virus (HIV). This article gives a review of the possible mechanisms associated with HIV lipodystrophy, namely HIV infection itself, genetic susceptibility to HIV lipodystrophy and effects of treatment with highly active antiretroviral therapy (HAART). Treating HIV lipodystrophy is challenging. The various treatment options currently available for treating lipodystrophy are reviewed.peer-reviewe

Pseudohyponatraemia : a literature review

Hyponatraemia often poses a diagnostic dilemma, brought about by inadequate work-up and inappropriate management. In order to make the correct diagnosis, an understanding of the pathophysiology and classification of hyponatraemia is essential. In this review, focus is made on the diagnosis of pseudohyponatraemia including the causes, when to suspect it and how to diagnose it. Different analytical methods are discussed, including flame emission spectrophotometry, and ion-specific electrode (ISE) potentiometry and the role they play in diagnosing pseudohypopatraemia. The measured and calculated osmolalities and their use to calculate the osmolal gap are explained. Finally, a discussion follows on the aetiologies of pseudohyponatraemia, strategies to circumvent this problem and the relevance of clinching the diagnosis in clinical practice.peer-reviewe

Approach to adrenal incidentalomas : a review

Adrenal tumours are nowadays most often discovered incidentally, on imaging not performed for suspected adrenal disease that are termed adrenal incidentalomas. There are two questions clinicians need to explore: whether the lesion is benign or malignant (relying mostly on radiology) and whether it is functional or not (relying on biochemical tests). An unenhanced CT scan (CT without contrast) or MRI is the imaging modality of choice. However if an incidentaloma is discovered on a CT with contrast, done for other reasons than suspected adrenal pathology, contrast washout may be helpful in diagnosing a benign lesion. Functional analysis in patients confirmed to have an adenoma or rarely an adrenal carcinoma should include tests to exclude cortisol excess, and in patients with hypertension mineralocorticoid excess. The production of subtle amounts of cortisol; not enough to cause classical clinical features of Cushing’s syndrome, but enough to cause metabolic disturbances and possibly increased mortality, has over recent years gained more attention. In those patients with suspected phaeochromocytoma, plasma free metanephrines or urinary fractionated metanephrines should be checked. This review, based on recent literature, discusses the evidence based suggested algorithms for investigating adrenal incidentalomas.peer-reviewe

Society for Endocrinology Endocrine Update 2019

A sixty-four-year old lady with a past medical history of total thyroidectomy for Graves’ disease and atrial fibrillation on amiodarone was referred to the endocrine out-patients in view of hypothyroidism. Since starting amiodarone, the TSH was noted to be elevated at 75 mU/l and the free T4 was 18 pmol/l. The patient complained of non-specific lethargy and was administered levothyroxine 50 mcg daily. Despite this her TSH remained elevated at 147 mU/l with a free T4 of 17.3 pmol/l and a free T3 of 2 pmol/l. TSH interference was ruled and a pituitary profile was normal. In the time of 2 years, despite gradual augmentation of her levothyroxine dose, the TSH remained elevated. At this point it was suspected that amiodarone might be causing type 1 5’ deiodinase enzyme inhibition leading to reduced peripheral conversion of T4 to T3. Hence the patient was commenced on a trial of liothyronine 12.5 mcg twice a day in addition to her levothyroxine. This eventually resulted in normalization of her thyroid function tests. Amiodarone induced hypothyroidism highlights the importance of life long thyroid function monitoring (free T3, free T4 and TSH) in patients on amiodarone. This case of amiodarone-induced hypothyroidism also reveals another possible indication for levothyroxine/liothyronine combination therapy.peer-reviewe

Presentation and management of diabetic ketoacidosis in adults in Malta

Aim: The aim of this audit was to assess adherence to local guideline in the management of Diabetic Ketoacidosis (DKA). Method: Patients admitted with DKA between April 2013 and March 2015 were identified and data was retrospectively collected from patients’ confidential files and Isoft®. Data collected included initial parameters recorded and biochemical investigations taken (initial and subsequent assessment of pH, HCO3-, blood glucose, potassium levels and urinary ketones), insulin regime started and intravenous fluid administered. Results: During the established time period 40 cases of DKA were identified in 18 patients. Median age was 33 years with a female preponderance of 60%. Six patients had newly diagnosed diabetes mellitus while 8 patients had more than one admission of DKA. All cases had capillary blood glucose monitoring (BGM) and/or venous random blood (plasma) glucose (RBG) checked and pH and HCO3- recorded on admission. 0.9% sodium chloride was the intravenous fluid started in all cases (as recommended by the guideline) and a median of 6.75L was prescribed during the first 24 hours. The median time spent on intravenous insulin infusion was 42.7 hours while the median time to pH >7.30, HCO3- >15mmol/L and negligible urinary ketones were 6.88, 12.83 and 34.5 hours respectively. Subcutaneous insulin was started at a median time of 48.21 hours from initiation of DKA protocol. Conclusion: This audit showed good adherence to local guideline. The great discrepancy between the time to pH >7.3 and the time to negligible urinary ketones highlights the need to introduce tools to measure systemic ketone production in the management of DKA with an update in the current local clinical practice guideline.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

An analysis of incidence and characteristics of Cushing's syndrome in Malta : a population based study

AIM: There are few reports discussing incidence and characteristics of the whole group of Cushing’s syndrome patients in the literature. The aim was to establish the incidence of endogenous Cushing’s syndrome with in-depth analysis of their various subtypes in a well-defined population.METHODS: Retrospective cross-sectional analysis of Cushing’s syndrome patients diagnosed between 2008 and 2017. A thorough search for patients was carried out in the central hospital registries including outpatients departments, surgical registries, radiological department and specialty clinic databases.RESULTS: 26 patients were identified as diagnosed with Cushing’s syndrome over the 10-year period equating to a standardised incidence rate (SIR) of 4.7/1,000,000/yr with an almost equal SIR among males and females. Analysing the various subtypes of Cushing’s syndrome, the majority (n = 13) were due to an ACTH secreting pituitary adenoma (SIR 2.5/1,000,000/yr). In this subtype males had a SIR of 3.4/1,000,000/yr compared to 1.7/1,000,000/yr in females. ACTH independent Cushing’s had a SIR of 1.8/1,000,000/yr with a strong female predominance (9:1) (SIR females: 3.0/1,000,000/yr; males: 0.5/1,000,000/yr). The SIR of ectopic ACTH secreting tumours was 0.4/1,000,000/yr. Interestingly hypokalaemia was present at diagnosis in those patients who harboured malignant causes for their Cushing’s syndrome (ectopic ACTH secreting tumours or adrenocortical carcinomas) and had markedly elevated cortisol levels at baseline compared to the rest (P < 0.001). Mean cortisol post overnight dexamethasone suppression testwas 1714 nmol/l (± 692 S.D.) in the malignant patients and 522 nmol/l (± 288 s.d.) in those patients with a benign tumour (P = 0.004). Mean ACTH values for Cushing’s disease patients was 110.4 (± 77.2 SD) pg/ml while in the ACTH independent group it was 5.5 (± 4.7 S.D.) pg/ml (P < 0.001).CONCLUSION: Cushing’s syndrome is a rare disease. Although the numbers are small, we could still establish distinct characteristics in the different subtypes.peer-reviewe

Epidemiology of PPGLs : a population based approach

Phaeochromocytoma/paragangliomas (PPGLs) are relatively rare tumours and the health burden of such tumours is not very well known.AIM: This population based study aims to characterise all the phaeochromocytomas, paragangliomas and adrenal medullary hyperplasia diagnosed between 2007 and 2016 in Malta; looking into presentation, hormonal analysis, imaging characteristics and histology findings.RESULTS: 16 patients were identified. 9 patients (56%) were males and age ranged from 21–62 years (mean 50±14). The standardised incidence rate is 4.3/1,000,000/year. From the whole cohort 11 (69%) had phaeochromocytomas confirmed histologically, 3 (19%) had paraganglioma, and another 2 patients (12%) had adrenal medullary hyperplasia (adrenal medullary cell mass hyperplasia <1 cm, thought to be a precursor of phaeochromocytoma). 9 patients (56%) presented with hypertension, whereas 6 patients (38%) were found following investigation of an adrenal incidentaloma. All patients except 1 had either plasma free metanephrines or urinary fractionated metanephrines checked prior to surgery. In the phaeochromocytoma and adrenal medullary hyperplasia patients, CT was documented to be suggestive of phaeochromocytoma or an adrenal lesion not in keeping with an adenoma in 11 out of 13 patients (85%). Longest radiological tumour size ranged from 20–127 mm (mean 52±28.9) All patients except 2 underwent surgical resection of the tumours. The latter 2 patients presented late with metastasis and died soon after diagnosis. Genetic testing was done in 6 patients (38%) and a VHL mutation was identified in one patient with phaeochromocytoma. 6 patients (38%) were found to have a malignant phaeochromocytoma on follow up.CONCLUSION: This review highlights the extensive workup needed for patients with PPGL. Presentation can range from asymptomatic to life threatening clinical conditions. The high risk of malignancy found in our cohort emphasizes the need for long term follow up.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