Hypopituitarism : a review on the diagnosis and management of central hypoadrenalism and hypothyroidism

A variety of conditions can result in hypopituitarism and this article focuses on the diagnosis, treatment and management of central hypoadrenalism and hypothyroidism. Central hypoadrenalism, if untreated, can potentially prove to be fatal and thus it is imperative that a timely diagnosis is done and life long supplementation instituted. Different glucocorticoid supplementation regimes together with possible side effects are discussed. Life long thyroxine replacement is needed for central hypothyroidism. Particular aspects regarding the diagnosis and management of central hypothyroidism are tackled. Important elements in the management of these patients, so as to ensure suitable supplementation are proper clinical and biochemical monitoring together with effective patient education.peer-reviewe

Diabetes in pregnancy : diagnosis, management, outcome and complications

Introduction: Numerous perinatal complications of diabetes in pregnancy have been recognised. Maternal post-partum complications can be equally devastating. Method: In this study, a cohort of known type 1 and type 2 pregnant diabetics and newly diagnosed Gestational Diabetes Mellitus (GDM) patients were analysed. Data collected was analysed in terms of method of diagnosis, gestational age at diagnosis for GDM, relevant medical or obstetric history, subsequent management and follow up. Results: Out of 79 viable pregnancies, 69.6% of patients were diagnosed with GDM, 13.9% with type 2 DM and 16.5% with type 1 DM. Mean gestational age for the GDM cohort was 37.9 (±1.6) weeks, 35.5 (±3.7) weeks in Type 2 and 37.1 (±0.7) weeks in the Type 1 cohort (p = 0.010). 20.3% of all cohort and specifically 23.6% of GDM pregnancies had a fetus which was large for gestational age. 30% of GDM patients, 25.5% of Type 2 DM patients and 84.6% of Type 1 DM patients, had their blood glucose controlled by an insulin infusion pump peri-partum. Mean HbA1C in the third trimester was 6.0%, 6.3% and 7.1% in GDM, Type 2 and Type 1 diabetics respectively (p = 0.004). A negative correlation was seen between HbA1C levels in third trimester and delivery gestational age (p < 0.001). Conclusion: Our findings emphasize the need for close follow up of these patients. Implementing a structured and holistic multidisciplinary team may have an impact on outcome, focusing on maternal education, in particular in GDM patients and their risk of developing type 2 DM in the future.peer-reviewe

Stroke patients' interpretation of symptoms and presentation to hospital

The aim of this study was to elucidate patient interpretation of stroke symptoms and to investigate factors which influence timely presentation to hospital. Methods: All patients admitted to Mater Dei Hospital with a diagnosis of cerebrovascular accident (CVA) or transient ischaemic attack (TIA) between July and September 2011 were recruited prospectively. Data was collected by patient interview and with reference to medical notes in order to determine patient risk factors for stroke, knowledge on stroke, interpretation of stroke symptoms and time interval to presentation to hospital. Results: The cohort studied (N=54) had an average age of 67.9 years (SD=10.407). The risk factors for cerebrovascular disease most frequently found in this group were hypertension (56\%), hypercholesterolaemia (56%), family history of stroke (41%) and smoking (39%). Participants interpreted their symptoms as stroke in 33% of cases (n=18), whereas 48% reported that they did not know or suspect any particular cause at the time. The perceived severity of events at symptom onset was reported as ‘high’ by 41% and ‘low’ by 57%. Only 31\% of participants (n=17) recognised the brain as the organ primarily affected in stroke. Forty five percent of patients sought medical advice within one hour. Fifty-six percent (n=30) first resorted to their family doctor, whilst 28% (n=15) phoned the emergency services. Family doctor as first contact was associated with delayed presentation (p = 0.007); conversely, phoning emergency services was associated with earlier presentation to A\&E. Conclusion: The results of this study highlight limited knowledge about stroke in the population involved. It also serves to clarify factors contributing to high rates of late presentation. These findings show the need for an improvement in public awareness in terms of education on stroke and the importance of early presentation to hospital.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

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

Society for Endocrinology Endocrine Update 2018

Water balance disorders following neurosurgery are well recognised and may give rise to both hypo- and hypernatraemia. We present the case of a 42-year-old male who developed a triphasic response after extended transsphenoidal surgery for a pituitary stalk lesion. The patient presented with a 4 month history of unremitting frontal headaches and dizziness. MRI confirmed a 15×15 mm stalk lesion. Clinical examination including formal visual perimetry was unremarkable. Blood tests revealed primary hypothyroidism but were otherwise normal. His past medical history included hypertension and alcoholism. He was referred to the UK where he underwent extended transsphenoidal surgery. In the immediate postoperative period, he developed polyuria (670 ml/h) and polydipsia (500 ml/h) which led to a negative fluid balance (of 2 L over 12 hours), serum sodium of 142 mmol/l, high serum osmolality of 299 mOsmol/kg and low urine osmolality of 131. The patient was normoglycaemic and did not receive any diuretics. Desmopressin (initally subcutaneous then desmotabs) reduced the polyuria and, together with intravenous fluids (2 L of 5% dextrose/day between days 1 and 2) and ad libitum drinking, restored normonatraemia. Hydrocortisone 10-5-5 mg was started on the 6th postoperative day in view of a morning cortisol of 25 nmol/l. On the 7th day post-op he developed severe SIADH with a serum sodium of 120 mmol/l, which was managed conservatively with fluid restriction (1.5 l/day). He was clinically euvolaemic, with normal kidney function (creatinine 53 Umol/l). Despite fluid restriction, fluid intake exceeded urine output (19 ml/h) producing a positive fluid balance of +1.5 l and a further fall in serum sodium to 119 mmol/l. Here the patient complained of headaches, unsteadiness and lethargy but no confusion or seizures. On day 12 the patient redeveloped polyuria (250 ml/hour) for which desmotabs 100mcgs daily were started. In anticipation of a triphasic response he was continued on ad libitum fluid intake and desmopressin was further increased to 100–200 mcgs as the patient was still waking up hourly to micturate. He was advised to omit one dose a week to allow excess water to be offloaded. On the 13th postoperative day he developed a serum sodium of 138 mmol/l, serum osmolality 299 mOsm/kg and urine osmolality of 79 mOsm/kg. Histology confirmed a pituicytoma (WHO grade 1); Ki-67 <1%.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

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

Society for Endocrinology Endocrine Update 2019

The patient is a 45 year old gentleman known case of HIV seropositivity (well-controlled, undetectable viral load) and polycystic kidney disease, who was referred to our Endocrine clinic by the Infectious disease specialists in view of a 4 year history of erectile dysfunction (ED – preceded diagnosis of HIV) and a low testosterone level. During the first consultation, the patient reported occasional lethargy and long term nausea which was attributed to his retroviral treatment. He denied any vomiting or headaches. The only neurology of note was right abducens nerve palsy, stable since diagnosis 10 years prior. (Magnetic resonance (MR) imaging of the head at time of initial presentation had been reported as showing no positive findings.) Clinical examination was otherwise unremarkable. A full pituitary profile taken after the initial endocrine consultation was suggestive of hypopituitarism (low serum total testosterone, cortisol and free thyroxine concentrations. In light of the biochemical investigations, an urgent MR pituitary was organised which showed an extensively infiltrating right parasellar lesion, which was most in keeping with a parasellar meningioma. A retrospective evaluation of his past imaging studies demonstrated that the lesion had already been present in the first MR study. Formal visual perimetry was overall normal. A standard short synacthen test (SST) performed after the results of the initial pituitary profile showed adequate cortisol response. He was subsequently started on testosterone and levothyroxine replacement therapy which brought about an improvement in his hypopituitary symptoms and biochemistry. At this point, definitive treatment of this gentleman’s meningioma is still being carefully evaluated within a multi-disciplinary team. Given the size and the location of the meningioma and the possible inherent complications of surgery, radiotherapy appears to be the favoured treatment option. This case report highlights the diagnostic pathway in the investigation of hypopituitarism whilst bringing to the fore mimickers of pituitary tumours.peer-reviewe