Prevalence and impact of diabetes and prediabetes on presentation and complications of primary hyperaldosteronism at diagnosis

BACKGROUND Primary hyperaldosteronism(PH)is considered to contribute to increased risk of developing type 2 diabetes mellitus(T2DM)and prediabetes.Both PH and DM are associated with increased risk for hypertension,cardiovascular diseases,and chronic kidney diseases.However,data on prevalence of T2DM and prediabetes in PH,and impact of T2DM and prediabetes on presentation and cardio renal complications in PH at presentation is sparse.AIM To determine the prevalence of T2DM and prediabetes in PH at diagnosis and impact on presentation and complications of PH.METHODS A retrospective cohort study was conducted in tertiary care settings in individuals with confirmed diagnosis of PH at presentation.Demographic variables,clinical presentations,duration and degree of hypertension,complications,laboratory parameters including sodium,potassium levels,plasma aldosterone concentration(PAC),plasma renin activity(PRA),and aldosterone to renin ratio(ARR)and cardio-renal parameters were collected.Comparison was done between three groups:PH with no DM(Group A)or with pre-diabetes(Group B)or with T2DM(Group C).P<0.05 was statistically significant.RESULTS Among 78 individuals with confirmed PH,62%had pre-diabetes or diabetes;with 37%having DM.Mean duration of T2DM was 5.97±4.7 years.The mean levels of glycaemic parameters among the group A vs B vs C individuals were fasting plasma glucose(mg/dL):87.9±6.5,105.4±9.02,130.6±21.1;post prandial plasma glucose(mg/dL):122.7±9.8,154.9±14,196.7±38.0;glycated haemoglobin(%)(5.3±0.2,5.9±0.2,7.5±0.6,P<0.05),respectively.There was no significant difference in the biochemical parameters(PAC,PRA,ARR,sodium,potassium levels),presentation and complications between the groups.Cardio renal parameters or degree and duration of hypertension were comparable between the groups.CONCLUSION Significant prevalence of T2DM and prediabetes in PH at diagnosis does not impact its presentation or complications.Early screening for undetected PH in T2DM and prediabetes subjects with hypertension may prevent complications.

Atractylenolide-I covalently binds to CYP11B2,selectively inhibits aldosterone synthesis, and improves hyperaldosteronism

Hyperaldosteronism is a common disease that is closely related to endocrine hypertension and other cardiovascular diseases. Cytochrome P450 11 B2(CYP11 B2), an important enzyme in aldosterone(ALD) synthesis, is a promising target for the treatment of hyperaldosteronism. However, selective inhibitors targeting CYP11 B2 are still lacking due to the high similarity with CYP11 B1. In this study,atractylenolide-I(AT-I) was found to significantly reduce the production of ALD but had no effect on cortisol synthesis, which is catalyzed by CYP11 B1. Chemical biology studies revealed that due to the presence of Ala320, AT-I is selectively bound to the catalytic pocket of CYP11 B2, and the C8/C9 double bond of AT-I can be epoxidized, which then undergoes nucleophilic addition with the sulfhydryl group of Cys450 in CYP11 B2. The covalent binding of AT-I disrupts the interaction between heme and CYP11 B2 and inactivates CYP11 B2, leading to the suppression of ALD synthesis;AT-I shows a significant therapeutic effect for improving hyperaldosteronism.

Management of hypertension in primary aldosteronism

Hypertension causes significant morbidity and mortal-ity worldwide, owing to its deleterious effects on the cardiovascular and renal systems. Primary hyperaldo-steronism(PA) is the most common cause of revers-ible hypertension, affecting 5%-18% of adults with hypertension. PA is estimated to result from bilateral adrenal hyperplasia in two-thirds of patients, and from unilateral aldosterone-secreting adenoma in approxi-mately one-third. Suspected cases are initially screened by measurement of the plasma aldosterone-renin-ratio, and may be confirmed by additional noninvasive tests. Localization of aldostosterone hypersecretion is then determined by computed tomography imaging, and in selective cases with adrenal vein sampling. Solitary adenomas are managed by laparoscopic or robotic re-section, while bilateral hyperplasia is treated with min-eralocorticoid antagonists. Biochemical cure following adrenalectomy occurs in 99% of patients, and hemo-dynamic improvement is seen in over 90%, prompting a reduction in quantity of anti-hypertensive medica-tions in most patients. End-organ damage secondary to hypertension and excess aldosterone is significantly improved by both surgical and medical treatment, asmanifested by decreased left ventricular hypertrophy, arterial stiffness, and proteinuria, highlighting the im-portance of proper diagnosis and treatment of primary hyperaldosteronism. Although numerous independent predictors of resolution of hypertension after adrenalec-tomy for unilateral adenomas have been described, the Aldosteronoma Resolution Score is a validated multifac-torial model convenient for use in daily clinical practice.

Endocrine hypertension:An overview on the current etiopathogenesis and management options

Endocrine causes of secondary hypertension include primary aldosteronism,pheochromocytoma,cushing's syndrome,hyperparathyroidism and hypo-and hyperthyroidism.They comprise 5%-10% of the causes of secondary hypertension.Primary hyperaldosteronism,the most common of the endocrine cause of hypertension often presents with resistant or difficult to control hypertension associated with either normo-or hypokalemia.Pheochromocytoma,a great mimicker of many conditions,is associated with high morbidity and mortality if left untreated.A complete history including pertinent family history,physical examination along with a high index of suspicion with focused biochemical and radiological evaluation is important to diagnose and effectively treat these conditions.The cost effective targeted genetic screening for current known mutations associated with pheochromocytoma are important for early diagnosis and management in family members.The current review focuses on the most recent evidence regarding causes,clinical features,methods of diagnosis,and management of these conditions.A multidisciplinary approach involving internists,endocrinologists and surgeons is recommended in optimal management of these conditions.

Conn’s Syndrome Secondary to Adrenal Adenoma

Primary hyperaldosteronism is not as uncommon as we thought, and by recent estimates the prevalance may be as high as 11% among hypertensives. We present a case of a 33 years old male patient came with a complaint of headache in occipital area & weakness in both lower limb since 4 weeks. The patient was a diagnosed case of hypertension and was already on tablet Atenolol (25 mg) once a day. At the time of admission, the patient was found to have a pulse of 96/min and blood pressure of 170/100 mm of Hg. Power was 3/5 for both right and left lower limbs. At the time of admission, serum potassium was 2.8. As a result, the patient was shifted to tablet Metroprolol and Amlodipine (50 + 5 mg) once a day. We also added tablet Cilnidipine (10 mg) and Telmisartan (80 mg) once a day and syrup Potklor thrice a day with water. The patient was sent for renal artery doppler, urine for metanephrines and vanillylmandelic acid, serum aldosterone, plasma aldosterone/plasma renin activity ratio (PAC/PRA ratio), urinary aldosterone, urinary cortisol and adrenocorticotrophic hormone level and computed tomography (CT) abdomen to rule out hyperaldostronism. Plasma aldosterone/plasma renin activity ratio, urinary aldosterone was high and CT abdomen revealed a solitary nodule in the left adrenal gland measuring 1.2 × 1.0 cm in maximum transverse diameter, which was suggestive of adrenal adenoma. Diagnosis of Conn’s syndrome secondary to adrenal adenoma was made. The patient was advised tablet Aldactone (25 mg) once a day and serum electrolytes were repeated which showed normalization with normal blood pressure.