How to Explore an Endocrine Cause of Hypertension

Hypertension (HTN) is the most frequent modifiable risk factor in the world, affecting almost 30 to 40% of the adult population in the world. Among hypertensive patients, 10 to 15% have so-called “secondary” HTN, which means HTN due to an identified cause. The most frequent secondary causes of HTN are renal arteries abnormalities (renovascular HTN), kidney disease, and endocrine HTN, which are primarily due to adrenal causes. Knowing how to detect and explore endocrine causes of hypertension is particularly interesting because some causes have a cure or a specific treatment available. Moreover, the delayed diagnosis of secondary HTN is a major cause of uncontrolled blood pressure. Therefore, screening and exploration of patients at risk for secondary HTN should be a serious concern for every physician seeing patients with HTN. Regarding endocrine causes of HTN, the most frequent is primary aldosteronism (PA), which also is the most frequent cause of secondary HTN and could represent 10% of all HTN patients. Cushing syndrome and pheochromocytoma and paraganglioma (PPGL) are rarer (less than 0.5% of patients). In this review, among endocrine causes of HTN, we will mainly discuss explorations for PA and PPGL.

NON-ALCOHOLIC FATTY LIVER DISEASE: WITH A FOCUS ON FRUCTOSE

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of fat in the liver in the absence of secondary causes. The review presents data on the role of fructose in the accumulation of fat in the liver and the mechanisms of NAFLD development. A number of data have been obtained on the effects of fructose, in the form of sugar-containing and fructose-containing drinks, related to NAFLD development.

Holocord spontaneous pneumorrhachis in the setting of refractory emesis

Background: Pneumorrhachis (PNR) is the presence of air within the spinal canal and may be either intramedullary or extramedullary in location. The etiology is most commonly iatrogenic or traumatic in nature. Treatment is dependent on underlying cause and physical exam. Case Description: Herein, we describe the second case in the literature of spontaneous holocord PNR in a young patient without risk factors. A 22-year-old male with no past medical history presented to the hospital for 2 days of vomiting and cramping in his hands and feet secondary to severe dehydration. He recently started a new job as a manual laborer and had to leave work early 2 days prior due to overexertion working outside in heat ranging from 100 to 120 degrees Fahrenheit. CT abdomen and pelvis demonstrated spontaneous pneumomediastinum and extramedullary PNR extending upward from L3 throughout the thoracic spine to the upper limit of the scan. Subsequent CT cervical and thoracic spine showed the full length of the extradural air from C2-T12 and again at L3. Conclusion: Spontaneous PNR is an uncommon, typically self-limited condition in which air is introduced into the spinal axis. Anatomic predisposition makes the extradural, dorsal cord in the cervicothoracic region the most common location. Patients are rarely symptomatic, and treatment is supportive in nature once secondary causes with high rates of morbidity and mortality are ruled out.

A 15 month - old Bangladeshi Baby With Very Severe Hypertriglyceridemia, Secondary to Glycogen Storage Disease

Hypertriglyceridemia is increasingly identified in children and adolescents, due to improved screening and higher prevalence of childhood obesity. The etiologic origin can be primary (genetic) or secondary, but it is often multifactorial. Management is challenging because of the interplay of genetic and secondary causes and lack of evidence-based guidelines. In this case report a fifteen month old boy was incidentally found with hypertriglyceridemia while finding the cause of his abdominal distension and was managed with oral and intravenous medications. KYAMC Journal. 2021;12(3): 182-186

rs779805 Von Hippel-Lindau Gene Polymorphism Induced/Related Polycythemia Entity, Clinical Features, Cancer Association, and Familiar Characteristics

Increased red blood cell count may result from primary erythrocytosis (polycythemia vera), but it is often due to secondary causes with increased erythropoietin levels. Secondary erythrocytosis may also be congenital due to different gene mutations of hemoglobin, hemoglobin stabilization proteins, EPO receptors, or oxygen sensing pathways. Von Hippel- Lindau gene mutation causes altered tissue oxygen sensation in VHL disease, usually with normal hemoglobin. Germline VHL mutations associate with classical VHL disease and represent genetic susceptibility for pheochromocytoma. VHL polymorphisms are mostly considered an innocent phenomenon. Still, some data indicate that these polymorphisms are not always harmless and can occur with prostate, renal, and colon cancer or even with isolated erythrocytosis. Seventy-eight patients referred to our department with elevated hemoglobin were screened for VHL mutations. There were no classical somatic VHL mutations. However, we found heterozygous (GA) or homozygous (AA) rs779805 VHL c.-195G>A polymorphism accompanied by erythrocytosis. These patients are Jak-2 negative, with normal or elevated EPO levels, sometimes with family accumulations and often phlebotomy needs, and in some cases with malignancies in the family. No other cause of erythrocytosis was found. We use phlebotomy regularly, and for those with cardiovascular risk factors, we recommend aspirin.

Diagnosis of idiopathic intracranial hypertension - the importance of excluding secondary causes: A systematic review

Background Idiopathic intracranial hypertension is characterized by increased intracranial pressure without any pathological findings on neuroimaging, except for signs of high intracranial pressure. Before diagnosing idiopathic intracranial hypertension secondary causes of increased intracranial pressure should be excluded. Objective to characterize the phenotype of patients with secondary intracranial hypertension and to identify possible risk factors for secondary intracranial hypertension. Methods We have systematically searched the PubMed database. The publications were analyzed according to the patient phenotype, age, gender, comorbidities, body mass index/weight status, and additional medication. The results are summarized in four categories: medication, infection, hormonal induced intracranial hypertension and miscellaneous groups of diseases related to sIH. Results We identified 105 eligible papers which included 272 cases. There were 49.6% pediatric cases. Among the adult group,70.9% were women. A total of 40.4% of all cases were obese or overweight, 27% among adults and 13.4% among pediatric cases. Increased BMI and recent weight gain, anemia, renal diseases and hypertension were the most frequent comorbidities related to sIH. Conclusion Among sIH patients, 40.4% were obese or overweight; two thirds were women. We recommend that even patients with a typical IIH phenotype should be screened for secondary causes.

Investigating Erythrocytosis: Changing Practice Patterns in the Era of Molecular Diagnostics

Background: Since the identification of JAK2 mutations in polycythemia vera (PV) in 2005 (Kralovics et al., NEJM 2005), molecular testing of JAK2 in patients with erythrocytosis has become part of routine clinical practice. We hypothesized that changes in the World Health Organization (WHO) diagnostic criteria for PV in 2016, which lowered the hemoglobin threshold to >165 g/L for men and >160 g/L for women, may have resulted in increased molecular testing. This study examines changing patterns of utilization of molecular diagnostics in patients referred for erythrocytosis at a tertiary care center. Methods: We examined all patients with erythrocytosis who underwent JAK2 testing, which included testing for JAK2 V617F with PCR between 2015 and 2017, and JAK2 V617F and exon 12 mutations with Next-Generation Sequencing (NGS) between 2018 and 2020 at London Health Sciences Centre in Ontario, Canada. We performed a retrospective chart review to extract laboratory and clinical data, including information on medical comorbidities and medications, with a focus on known secondary causes of erythrocytosis. Results: A total of 668 patients with erythrocytosis underwent JAK2 testing at our institution between August 1, 2015 and December 31, 2020. There was an overall increase in testing over the five-year study period, with a decline in the positive detection rate: 8/29 (28%) in 2015, 15/94 (16%) in 2016, 15/100 (15%) in 2017, 19/136 (14%) in 2018, 17/162 (10%) in 2019, and 14/147 (10%) in 2020 (Figure 1). The average hemoglobin levels in patients with erythrocytosis who underwent testing remained similar across all years (range 170-173 g/L for women, 179-181 g/L for men). In our cohort, there was a high proportion of patients with known or suspected secondary causes of erythrocytosis who underwent molecular testing. Between 2018 and 2020, 324/445 (73%) of patients who underwent molecular testing had either chronic obstructive pulmonary disease, obstructive sleep apnea, other hypoxic lung disease, smoking history, erythropoietin-secreting tumor, or potential drug-induced erythrocytosis. Specifically, we observed an increase in proportion of patients who underwent molecular testing on sodium-glucose cotransporter-2 (SGLT-2) inhibitors, a known secondary cause of erythrocytosis, with 15/136 (11%) in 2018, 17/162 (10%) in 2019, and 25/147 (17%) in 2020. In contrast, the proportion of patients on testosterone was relatively constant at 15/136 (11%) in 2018, 11/162 (6.8%) in 2019, and 11/147 (7.5%) in 2020. Conclusion: This study revealed that a high proportion of patients with known or suspected secondary causes of erythrocytosis underwent JAK2 testing, resulting in increase in molecular testing over time and a decline in positive detection rate. In particular, we observed a number of patients on SGLT-2 inhibitors who had investigation, suggesting that this class of medications may be an underrecognized cause of drug-induced erythrocytosis (Chin-Yee et al., CMAJ 2020). Our findings underscore the importance of careful medical history and medication review to support more judicious use of molecular testing. Similarity in average hemoglobin levels across the five-year study period suggests that other factors, such as increased availability of 'routine' molecular testing, rather than changes in the WHO diagnostic criteria may explain increases in JAK2 testing. Our study indicates a need to develop an effective clinical prediction rule for JAK2 positivity to better risk stratify patients with suspected PV based on clinical and laboratory parameters to optimize utilization of molecular diagnostics. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Secondary Headache Disorders

In the evaluation of a patient with headache, the first task is to differentiate between a secondary headache and a primary headache. This step is essential because secondary causes of headache may require vastly different evaluation and treatment than primary headache disorders. Thunderclap headache (TCH) is an acute, severe headache with an abrupt onset, reaching maximum intensity in less than 1 minute. TCH is a neurologic emergency and should immediately prompt an urgent evaluation for a secondary headache.