Endocrine Hypertension

Presenter:
Dr D Shree Bhushan Raju
• India – Heading towards the “hypertension capital” of the world

• High prevalence, younger population getting affected

• Poorly managed - about 70% patients do not reach BP goal

https://www.adityabirlacapital.com/healthinsurance/active-together/2019/05/27/high-blood-pressure-in-india/
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COVID-19 Hypertension
Deaths
Silent Killer
Deaths
In 2 years In 1 year

https://www.dnaindia.com/health/report-dna-special-why-hypertension-or-high-blood-pressure-is-the-silent-killer-2890750
Major Complications
Hypertension
Classification
Primary and Secondary causes of hypertension
Many hypertensive patients remain untreated or do not achieve BP
control (NHANES)

untreated failed to achieve BP control*

Percentage of population

**
**

* BP control defined as BP < 140/90 mmHg; BP < 130/80 mmHg for patients with diabetes or CKD;
includes treated and untreated patients, except ** (only treated patients)

Chobanian et al. Hypertension. 2003;42:1206–1252; Ong et al. Hypertension. 2007;49:69–75;

Ostchega et al. NCHS Data Brief. 2008;3:1–38;
Egan et al. JAMA. 2010;303:2043–2050.
 Resistant Hypertension: A Subset of Hypertension

Nephrology self-assessment program: NephSAP (2014) 13(2):57-63

 Resistant Hypertension

• Blood pressure above

goal on 3 medications of
different classes as per
ACC/AHA 2017
• One of these medications
should be a diuretic
• If control on 4 drugs, this
is also resistant
hypertension
 Endocrine Hypertension
Secondary hypertension, a term used for the hypertension for which there is an identifiable
cause, accounts for 10% of all patients with hypertension.

Endocrine conditions as a cause of secondary hypertension comprise 5%–10% of all patients

with hypertension

The endocrine conditions causing secondary hypertension are primary aldosteronism,

pheochromocytoma, Cushing’s Syndrome, acromegaly, hyperparathyroidism, congenital
adrenal hyperplasia, hypothyroidism, hyperthyroidism and renin-secreting tumors.

Factors that should prompt a referral are young hypertensive patients (< 30 years of age); a
positive aldosterone-to-renin ratio with elevated aldosterone level; and > 30% rise in serum
creatinine level after initiation of an ACE inhibitor or ARB, or discrepant kidney size.
World J Hypertens. 2015 ; 5(2): 14–27. doi:10.5494/wjh.v5.i2.14
Endocr Rev, Volume 38, Issue 2, 1 April 2017, Pages 103–122, https://doi.org/10.1210/er.2017-00054
The content of this slide may be subject to copyright: please see the slide notes for details.
Endocrine Causes of Hypertension - Clinical
Presentation - Diagnostic Tools
 1. Primary Hyper-aldosteronism

One of the most Recommended that this

Accounts for 5-13% of
common causes of be considered in the
the population with age
secondary hypertension, differential diagnosis of
of onset between 30
increasingly recognized uncontrolled
and 60
disease hypertension patients

Exists in several forms: IHA involves bilateral adrenals and accounts for an
estimated 60%–66% of diagnosis.
Idiopathic Aldosterone
hyperaldosteronism producing APA, the classic case first discovered by Conn over 60
(IHA) adenoma (APA) years ago, is a unilateral adrenal adenoma and makes
up most remaining cases of primary
hyperaldosteronism (30%–35%)
World J Hypertens. 2015 ; 5(2): 14–27. doi:10.5494/wjh.v5.i2.14
 1. Primary Hyper-aldosteronism – Clinical Presentation

• Presents with difficult to control

hypertension and hypokalemia

• If severe, hypokalemia may be

accompanied by muscle
weakness, cramping, headaches,
palpitations and polyuria

• Hypokalemia may be unmasked

with the addition of diuretics
• Many patients may present
without hypokalemia

World J Hypertens. 2015 ; 5(2): 14–27. doi:10.5494/wjh.v5.i2.14

Screening for PAH should be considered for hypertensive patients with
the following presentation:
• hypokalemia, difficult to control hypertension on 3 or more anti-
hypertensive drugs or hypertension of ≥ 160 mmHg systolic and ≥ 100
mmHg diastolic
• those with hypertension and an incidental adrenal mass
• young onset of hypertension, or those being evaluated for other
causes of secondary hypertension
• those with hypertension and diuretic-induced hypokalemia
• those with family history of early onset hypertension or stroke at age <
40
• all hypertensive patients with a first degree relatives of those with
primary hyperaldosteronism
World J Hypertens. 2015 ; 5(2): 14–27. doi:10.5494/wjh.v5.i2.14
 Primary
Hyper-
aldosteronism

Screening /
treatment

https://www.researchgate.net/figure/Algorithm-for-diagnosis-
and-management-of-Primary-Aldosteronism-from-reference-11-
with_fig1_267732757
 2. Pheochromocytoma
Tumor of the adrenal
medulla (Chromaffin cells) Pheochromocytomas and
that secretes excess catecholamine secreting Both the tumors have
catecholamines, paragangliomas account for similar clinical presentation
epinephrine, nor- 0.2-0.6% of all hypertension
epinephrine and dopamine
 2. Pheochromocytoma – Clinical Presentation

• Occurrence age – 40-50 years,

equally distributed between males
and females

• Classic triad of symptoms – episodic

headache, sweating, tachycardia –
may not always be present in most
patients

• Most common signs – sustained

hypertension, paroxysmal
hypertension, normotension (5-15%
patients)
2. Pheochromocytoma – Clinical Presentation
2. Pheochromocytoma – Management
 2. Pheochromocytoma – Medical Management

• Main goal of therapy includes – normalization of blood pressure, heart rate,

restores volume depletion and prevention of intra-operative hypertensive
crisis
• Phenoxybenzamine – long lasting, non-selective, irreversible, non-competitive
alpha blocker – reduces BP fluctuations, eases vaso-constriction and prevents
intra-operative hypertensive crisis
• Starting dose – 10mg BID, with increments of 10-20mg every 2-3 days
• Other short acting alpha blockers include – doxazosin, prazosin
• Once optimal α-blockade is achieved, β-blockers are used for the
management of catecholamine-induced tachyarrhythmias.
• Calcium channel blockers (Nifedipine, Verapamil) are the second line anti-
hypertensive medications use to supplement α-blockers
3. Congenital adrenal
hyperplasia

Congenital Adrenal
Hyperplasia
• Adrenal enzyme defect
• ACTH drives precursors
• Not in deficiency 21
hydroxylase = not HTN
• Low Renin and
Aldosterone in
hypertension
3. Congenital adrenal hyperplasia – Diagnosis and emergency treatment
4. Cushing’s Syndrome
• Cushing’s disease is caused by endogenous
hypercortisolism. This is due to the
hypersecretion of the adrenocorticotropic
hormone (ACTH) by an ACTH secreting
pituitary adenoma

• The prevalence of Cushing’s disease is of

40:1,000,000 people and more often occurs
in women (sex ratio of 9:1 in favor of
women)

• Cushing’s disease is associated with an

increased risk of cardiovascular and
metabolic manifestations, as well as
respiratory disorders, psychiatric
complications, osteoporosis and infections,
all
 4. Cushing’s Syndrome - Symptoms

• 50% of the patients with Cushing’s disease have pituitary microadenoma with a diameter smaller than 5 mm,
which are difficult to see through imaging investigation (Computer Tomography and Magnetic Resonance)

• Weight gain, generalized in 50% of the cases or sometimes with centripetal fat distribution, especially on the
trunk, abdomen, interscapular (“buffalo hump”) supraclavicular fat pat, round plethoric face (“moon face”)

• Hypertension thin skin, easy bruising, capillary fragility, purplish-red striae (thighs, flanks, lower abdomen, upper
limb root, breasts), acne, flushing, fungal skin infections, poor healing of skin wounds lower limb edema,
hypotrophy and proximal limb muscle fatigue, impaired glucose tolerance or type 2 diabetes, osteopenia or
osteoporosis with pathological vertebral compression fractures, aseptic necrosis of the femoral head
hyperpigmentation of the skin and mucous membranes, a consequence of the ACTH-MSH cross reactivity, which
occurs in high levels of ACTH (in Cushing’s disease and non Cushing’s syndrome) or in the secretion of ectopic
ACTH (also Nelson syndrome)

Journal of Medicine and Life Vol. 9, Issue 1, January‐March 2016
4. Cushing’s Syndrome – Treatment
4. Cushing’s Syndrome – Treatment (New Advances)
 The significance of recognizing rare causes of hypertension

Left undiagnosed, secondary hypertension can lead to resistant hypertension,

cardiovascular and renal complications, multiple specialist referrals and an
unnecessary burden on the healthcare system

Identifying and treating the cause can potentially cure or markedly improve
hypertension and reduce the associated cardiovascular risk

Singapore Med J 2016; 57(5): 228-232 doi: 10.11622/smedj.2016087

Extra slides
 Medications that can interfere with BP control

HypertensionVolume 51, Issue 6, 1 June 2008; Pages 1403-1419

https://doi.org/10.1161/HYPERTENSIONAHA.108.189141
 Treatment – Resistant HTN

1. Withdrawal of Interfering Medications

• Medications that may interfere with blood pressure control, particularly NSAIDs,
should be avoided or withdrawn in patients with resistant hypertension.
• However, as this is often clinically difficult, the lowest effective dose should be
used with subsequent down titration whenever possible.
• Like other nonnarcotic analgesics, acetaminophen is associated with an increased
risk of developing hypertension, although when compared with ibuprofen it was
less likely to worsen blood pressure control in treated subjects.
• Therefore, if analgesics are necessary, acetaminophen may be preferable to
NSAIDs in subjects with resistant hypertension, recognizing, however, that
acetaminophen will provide little if any anti-inflammatory benefit.

HypertensionVolume 51, Issue 6, 1 June 2008; Pages 1403-1419

https://doi.org/10.1161/HYPERTENSIONAHA.108.189141
 Treatment – Resistant HTN

2. Combination Therapy
• A triple drug regimen of an ACE inhibitor or ARB, calcium channel blocker,
and a thiazide diuretic is effective and generally well tolerated. This triple
regimen can be accomplished with 2 pills with use of various fixed-dose
combinations.
• Potent vasodilators such as hydralazine or minoxidil can be very effective,
particularly at higher doses, but adverse effects are common. With
minoxidil especially, reflexive increases in heart rate and fluid retention
occur such that concomitant use of a β-blocker and a loop diuretic is
generally necessary.

HypertensionVolume 51, Issue 6, 1 June 2008; Pages 1403-1419

https://doi.org/10.1161/HYPERTENSIONAHA.108.189141