European Journal of Cardiovascular Medicine

Hypertension is defined as a systolic blood pressure of over or equal to 140mmHg, and diastolic blood pressure over or equal to 90mmHg measured ideally after 30-45 mins of rest and in a calm environment, with individual sitting quietly, preferably 3 recordings, with adequate size cuff and closest to heart, interpreted by the same observer for the 3 reading according to latest European Society Guidelines for Hypertension (ESH)⁽¹⁾.90 percent of cases are due to no cause and is called Primary/ Essential Hypertension. Rest 10 percent are attributable to systemic causes and include, a broad category called Secondary hypertension⁽²⁾.Secondary endocrine hypertension accounts for 5-12% of hypertension’s causes. In selected patients (type 2 diabetes mellitus, sleep apnea syndrome with resistant hypertension, sudden deterioration in hypertension control), prevalence could be higher. Rest of the causes are either renal/ Vascular⁽³⁾⁽⁶⁾.Of the endocrine causes – Primary Hyperaldosteronism accounts for the most, followed in frequency by Cushings and Pheochromocytoma^(4)(13). Rarer monogenic forms include- Apparent mineralocorticoid excess, Gordon syndrome and Liddle syndrome, Glucocorticoid remediable Hyperaldosteronism (GRE)^(7)(12).

Study design:Cross Sectional Study

Place of study: This study was conducted at General Medicine Department ,King George Hospital,Visakhapatnam, Andhra Pradesh.

Duration of study: September 2022- June 2023 ( 9 months)

Sample population: 80 subjects – 40 cases and 40 controls who were admitted in the medical wards of King George Hospital,Visakhapatnam.

Selection Criteria:

Inclusion criteria:

1. Patients aged  below  40 years
2. Patients with atleast 3 recordings suggestive of Hypertension.
3. Patients in whom Cardiac and Renal causes of hypertension have been ruled out.

Exclusion criteria:

• Hypertensives aged above 40 and below 12 years.
• Patients on Antihypertensive medication prior to admission to King George Hospital.

METHODOLOGY :

The present study was undertaken after obtaining approval from Institutional Ethics Committee (IEC). Prior informed consent was taken from all the subjects enrolled in the study. Subjects who fulfilled selection criteria were taken as cases (study group).

Apparently healthy subjects (matched for age, sex) were included as a control group. Patients visiting OP or admission with recording of Blood Pressure atleast 3 times after 30-45 mins of rest, using a manual sphygmomanometer, with appropriate size cuff tied over left upper arm near to heart in sitting position.

 Cutoff for Hypertension taken as >140/90mmHg.

Complete history was taken and detailed physical examination was done.

Once labelling a patient as hypertensive, the following investigations were done after  taking  informed  consent.

Serum cortisol, Plasma catecholamines, Serum renin, Serum Aldosterone  24hr urine metanephrines and VMA ( in selected few).

Imaging techniques ( MRI abdomen/ USG abdomen) – in selected few.

Reports were obtained and then statistical analysis was carried out using unpaired t test. Results were expressed with respect to ‘p’ value, mean and standard deviation and were being interpreted.

1. Of the endocrine causes of Hypertension, primary Hyperaldosteronism accounted for the most common cause, followed by Cushings syndrome and third byPheochromocytoma.
2. Rare causes accounted for less than 1 percent of cases and to diagnose such entities, genetic screening tests and limitation of resources, and financial restraints were taken into account.

EndocrineHypertension

• Primary Hyperaldosteronism(PH) – Any problem that lies within the adrenal cortical zona glomerulosa, be it – adrenal cortical hyperplasia/ adenoma/ functioning carcinoma is of primary in origin.

Tools required for diagnosis of PH are

1.USG abdomen

2.CECT/MRI Abdomen ( visualise suprarenal masses)

3.Orthostatic Aldosterone in serum

4.Plasma Renin

5.Plasma Renin / Aldosterone Ratio.

• A PAC ratio of more than 1 is suggestive of a primary etiology.
• Among PH- Hyperplasia> Adenoma> Carcinoma in order of frequency.
• Cushings syndrome is due to a defect either in the zona fasciculata within the adrenal gland / secondary – due to a

  ACTH secreting pituitary adenoma/ ACTHrp releasing Paraneoplastic tumor/ due to exogenous corticosteroids.

• Cushings Disease is the term given to cases due to pituitary adenoma. Irrespective of the causes, an early morning serum cortisol in the fasting state is collected from patients and a low dose dexamethasone suppression test done at 11pm the night prior to sample collection are done and the high levels irrespective of negative feedback are suggestive of hypercortisolism.
• Further studies to delineate subtypes of hypercortisolismrequire a pituitary imaging, high dose dexamethasone suppression test and inferior petrosal vein sampling but in depth evaluation is not taken into consideration in our study.
• Pheochromocytoma – Though less common than the above 2, it presents with varying symptoms that ultimately lead to a diagnosis once all other causes are excluded. It is due to hyperfunctioning adrenal medulla that releases catecholamines – Noradrenaline, Adrenaline and Dopamine- and these chemicals are activators of Sympathetic nervous system hence symptoms are pertaining to excess sympathetic activity.
• Plasma catecholamines measurement is cumbersome, but informed consent from limited number of patients allowed for further testing for Pheochromocytoma in some patients based on certain clinical features.
• 24hr urine metanephrines and VMA have been tested in those in whom PH and Cushings were excluded and those with significant levels were noted.

Non Endocrine Causes of Secondary Hypertension

• Renal causes account for most cases among young children and adolescents like- B/L renal artery stenosis, Fibromuscular dysplasia, Nephrosclerosis.
• Cardiac and Vascular causes include coarctation of aorta, vasculitis, and systemic hypertension.
• However all such causes have been excluded from the study as well as those with Essential Hypertension.

• Of the endocrine causes of Hypertension, primary Hyperaldosteronism accounted for the most common cause, followed by Cushings syndrome and third by Pheochromocytoma.
• Rare causes accounted for less than 1 percent of cases and to diagnose such entities, genetic screening tests and limitation of resources, and financial restraints were taken into account.

1. Fagugli RM, Taglioni C. Changes in The Perceived Epidemiology of Primary Hyperaldosteronism. Int J Hypertens. 2011:162804–162804. [PMC free article] [PubMed] [Google Scholar]
2. Moraitis A, Stratakis C. Adrenocortical Causes Of Hypertension. Int J Hypertens. 2011:624691–624691. [PMC free article] [PubMed] [Google Scholar]
3.  Al-Salamis A, Cohen R, Chanson P, et al. Update on Endocrine Hypertension. Article in French. Ann Endocrinol (Paris) 2012;73(Suppl1):S26–S35. [PubMed] [Google Scholar]

4. Mukherjee JJ, Khoo CM, Thai AC, et al. Type 2 Diabetic Patients with Resistant Hypertension should be Screened For Primary Aldosteronism. Diab Vasc Dis Res. 2010;7:6–13. [PubMed] [Google Scholar]
5. Di Murro A, Petramala L, Cotesta D, et al. Renin-Angiotensin-Aldosterone System in Patients with Sleep Apnoea: Prevalence of Primary Aldosteronism. J Renin Angiotensin Aldosterone Syst. 2010;11:165–172. [PubMed] [Google Scholar]
6. Cicala MV, Mantero F. Hypertension in Cushing’s Syndrome: From Pathogenesis to Treatment. Neuroendocrinology. 2010;92(1):44–49. [PubMed] [Google Scholar]
7. Martins LC, Conceicao FL, Muxfeldt ES, et al. Prevalence and Associated Factors of Subclinical Hypercortisolism in Patients with Resistant Hypertension. J Hypertens. 2012;30:967–973. [PubMed] [Google Scholar]
8. Chiodini I, Morelli V, Salcuni AS, et al. Beneficial Metabolic Effects of Prompt Surgical Treatment in Patients with an Adrenal Incidentaloma Causing Biochemical Hypercortisolism. J Clin Endocrinol Metab. 2010;95:2736–2745. [PubMed] [Google Scholar]
9. Prejbisz A, Lenders JW, Eisenhofer G, et al. Cardiovascular Manifestations of Phaeochromocytoma. J Hypertens. 2011;29:2049–2060. [PubMed] [Google Scholar]
10. Funder JW, Carey RM, Fardella C, et al. Case Detection, Diagnosis and Treatment of Patients with Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93:3266–3281. [PubMed] [Google Scholar]