Successful medical management of insulinoma with diazoxide for 27 years

Summary: Despite improvements in localisation techniques and surgical advances, some patients with insulinoma will not be cured by surgery or may not be suitable for surgery. Medical management with diazoxide is an option for such cases. This case report details 27 years of successful management of insulinoma using diazoxide. It has been effective and safe, with only minor adverse effects. Learning points: Long term diazoxide use can be a safe, effective option for insulinoma when it cannot be localised or removed surgically. Common adverse effects include peripheral oedema, hyperuricaemia, and hirsutism. 68Ga-NOTA-exendin-4 PET/CT scan should be considered for insulinoma localisation when other modalities have been unhelpful

Persistent syndrome of inappropriate antidiuretic hormone secretion following traumatic brain injury

UNLABELLED: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) can occur following traumatic brain injury (TBI), but is usually transient. There are very few case reports describing chronic SIADH and all resolved within 12 months, except for one case complicated by meningo-encephalitis. Persistent symptomatic hyponatremia due to chronic SIADH was present for 4 years following a TBI in a previously well 32-year-old man. Hyponatremia consistent with SIADH initially occurred in the immediate period following a high-speed motorbike accident in 2010. There were associated complications of post-traumatic amnesia and mild cognitive deficits. Normalization of serum sodium was achieved initially with fluid restriction. However, this was not sustained and he subsequently required a permanent 1.2 l restriction to maintain near normal sodium levels. Multiple episodes of acute symptomatic hyponatremia requiring hospitalization occurred over the following years when he repeatedly stopped the fluid restriction. Given the ongoing nature of his hyponatremia and difficulties complying with strict fluid restriction, demeclocycline was commenced in 2014. Normal sodium levels without fluid restriction have been maintained for 6 months since starting demeclocycline. This case illustrates an important long-term effect of TBI, the challenges of complying with permanent fluid restrictions and the potential role of demeclocycline in patients with chronic hyponatremia due to SIADH. LEARNING POINTS: Hyponatraemia due to SIADH commonly occurs after TBI, but is usually mild and transient.Chronic hyponatraemia due to SIADH following TBI is a rare but important complication.It likely results from damage to the pituitary stalk or posterior pituitary causing inappropriate non-osmotic hypersecretion of ADH.First line management of SIADH is generally fluid restriction, but hypertonic saline may be required in severe cases. Adherence to long-term fluid restriction is challenging. Other options include oral urea, vasopressin receptor antagonists and demeclocycline.While effective, oral urea is poorly tolerated and vasopressin receptor antagonists are currently not licensed for use in Australia or the USA beyond 30 days due to insufficient long-term safety data and specific concerns of hepatotoxicity.Demeclocycline is an effective, well-tolerated and safe option for management of chronic hyponatraemia due to SIADH

Thyroid-Hormone Uptake by Hepatocytes - Structure-Activity-Relationships of Phenylanthranilic Acids with Inhibitory Activity

The synthesis of a series of mono- and disubstituted N-phenylanthranilic acids is described. Substituents on the phenyl ring include Cl, CN, OH, CF3, Br, I, CH3, OCH3, and OCF2CF2H. These compounds have been tested for their inhibitory effect on triiodothyronine (T3) uptake by H4 hepatocytes. The nonsteroidal antiinflammatory drugs flufenamic acid, mefenamic acid, and meclofenamic acid and the structurally related compounds 2,3-dimethyldiphenylamine and diclofenac were also tested. The most potent compounds were found to be, in order of decreasing activity, meclofenamic acid (2,6-Cl2,3-CH3), flufenamic acid (3-CF3), mefenamic acid (2,3-(CH3)2), and the compounds with 3,5-Cl2 and 3-OCF2CF2H substituents. The least potent compounds had 3-CN and 3-OH substituents. An analysis of quantitative structure-activity relationships (QSAR) for the series of phenylanthranilic acids showed that the inhibition of T3 uptake is highly dependent on the hydrophobicity of the compound. The relationship between uptake inhibition and the calculated octanol-water partition coefficient (clogP) was found to be parabolic, with optimum inhibitory activity found when the clogP of the phenylanthranilic acid was 5.7. It was also found that the 1-carboxylic acid group of the phenylanthranilic acids was not a prerequisite for uptake inhibition to occur, but its removal or alteration resulted in reduced inhibition

Intense pulsed light treatment of chronic mid-body Achilles tendinopathy: A double blind randomised placebo-controlled trial.

We conducted a randomised controlled trial to determine whether active intense pulsed light (IPL) is an effective treatment for patients with chronic mid-body Achilles tendinopathy. A total of 47 patients were randomly assigned to three weekly therapeutic or placebo IPL treatments. The primary outcome measure was the Victorian Institute of Sport Assessment - Achilles (VISA-A) score. Secondary outcomes were a visual analogue scale for pain (VAS) and the Lower Extremity Functional Scale (LEFS). Outcomes were recorded at baseline, six weeks and 12 weeks following treatment. Ultrasound assessment of the thickness of the tendon and neovascularisation were also recorded before and after treatment. There was no significant difference between the groups for any of the outcome scores or ultrasound measurements by 12 weeks, showing no measurable benefit from treatment with IPL in patients with Achilles tendinopathy

Fine needle aspiration and medullary thyroid carcinoma: the risk of inadequate preoperative evaluation and initial surgery when relying upon FNAB cytology alone.

OBJECTIVES: To evaluate the diagnostic accuracy of fine-needle aspiration biopsy (FNAB) to preoperatively diagnose medullary thyroid cancer (MTC) among multiple international centers and evaluate how the cytological diagnosis alone could impact patient management. METHODS: We performed a retrospective chart review of sporadic MTC (sMTC) patients from 12 institutions over the last 29 years. FNAB cytology results were compared to final pathologic diagnoses to calculate FNAB sensitivity. To evaluate the impact of cytology sensitivity for MTC according to current practice and to avoid confounding results by local treatment protocols, changes in treatment patterns over time, and the influence of ancillary findings (e.g., serum calcitonin), therapeutic interventions based on FNAB cytology alone were projected into 1 of 4 treatment categories: total thyroidectomy (TT) and central neck dissection (CND), TT without CND, diagnostic hemithyroidectomy, or observation. RESULTS: A total of 313 patients from 4 continents and 7 countries were included, 245 of whom underwent FNAB. FNAB cytology revealed MTC in 43.7% and possible MTC in an additional 2.4%. A total of 113 (46.1%) patients with surgical pathology revealing sMTC had FNAB findings that supported TT with CND, while 37 (15.1%) supported TT alone. In the remaining cases, diagnostic hemithyroidectomy and observation were projected in 32.7% and 6.1%, respectively. CONCLUSION: FNAB is an important diagnostic tool in the evaluation of thyroid nodules, but the low sensitivity of cytological evaluation alone in sMTC limits its ability to command an optimal preoperative evaluation and initial surgery in over half of affected patients