Talk on Endocrine causes of Hypertension delivered on 23rd June 2017 at BAPS Hospital, Vadodara

1. APPROACH TO HYPERTENSION IN
YOUNG
‘ENDOCRINOLOGIST PERSPECTIVE’
DR. OM J LAKHANI
MD, DNB (ENDOCRINE)
CONSULTANT ENDOCRINOLOGIST
ZYDUS HOSPITAL, AHMEDABAD
Phone- +919871009021

2. Consultation Details
• Timings 10 am t0 1 pm and 4 pm to 7 pm
from Monday to Saturday
• Zydus Hospitals, Ahmedabad
• Phone – 079-6619 0201
• Email – dromlakhani@gmail.com

3. Imp Information
• Images of the patients have been removed

4. Introduction to the Talk
1. Mainly discuss 5 Cases of Endocrine causes
of hypertension
2. Stick to practical and clinically relevant
points

5. CASE #1

6. • 25 year old male
• Pre-employment checkup
• BP – 150 / 100 mm Hg
• Does this patient need evaluation for
secondary hypertension ?

7. • Q. In Which cases would you consider
secondary cause of hypertension ?

8. 1. Resistant Hypertension
2.Hypertension in patient
<30 years or childhood
3.Malignant or accelerated
hypertension

9. • Q. What are the Major causes of Secondary
Hypertension ?

10. RENAL
• Renovascular
Hypertension
• Primary Renal disease

11. ENDOCRINE CAUSES
• Primary
Aldosteronism
(Conn’s syndrome)
• Cushing’s Syndrome
• Pheochromocytoma
• Other Endocrine
causes

12. CARDIOVASCULAR CAUSES
• Coarctation of the
aorta

13. • Q. What Investigations we generally order
when dealing with a secondary hypertension
?

14. Our List of Investigations
*Sir Ganga Ram Hospital Protocol for
Secondary Hypertension
1. Apart from Routine investigations (as
appropriate)
2. S. Creatinine
3. S. Electrolytes- Calcium, Sodium, Potassium,
Bicarbonate
4. Thyroid function test
5. 24 hr Urine Metanephrine and
Normetanephrine
6. Aldosterone – Renin Ratio
7. Ultrasound of Abdomen and Pelvis

15. CASE #2

16. • 35 year old male
• Hypertension
• Weight gain
• Change in Mood
• Stretch marks over abdomen

18. • Q. What is the SPOT Diagnosis ?

19. • Cushing’s syndrome

20. • Q. Based on clinical examination, in Which
cases would you consider testing for
Cushing’s syndrome ?

21. • Facial Flushing
• Violaceous striae in Abdomen
• Proximal Muscle weakness

24. • Q. How will you Diagnose Cushing’s
syndrome ?

25. • For Diagnosis of Cushing’s syndrome , we
need to have TWO tests for Cushing’s
syndrome positive.

26. SGRH Protocol for Cushing’s
diagnosis
DAY 1
1. 8 am Cortisol – to rule out Exogenous Cushing’s
syndrome
2. Collect Sample for S. Cortisol at 11 pm and ACTH
(Late night serum cortisol)
3. Then give 1 mg of Dexamethasone
DAY 2
1. Again collect S. Cortisol at 8 am the next morning
Points 2 and 3 – Overnight Dexamethasone suppression
test

27. • Late night Serum cortisol >7.5 mcg/dl –>
Suggestive of Cushing’s
• After ONDST – Serum cortisol >1.8 mcg/dl –
diagnostic of Cushing’s
• 8 am cortisol on day 1 if <3.6 mcg/dl –
suggestive of Exogenous Cushing’s

28. Alternative Approach
• Day 1 – 24 hr urine free cortisol
• Day 2 – ONDST
24 hr urine free cortisol normal range is 80-120
mcg/24

29. Caution !
• Make sure you DON’T start collection of 24
hr UFC , after giving Dexamethasone for
ONDST

30. • Q. Diagnosis of Cushing’s is Established ,
what next ?

32. Before & After

33. CASE #3

34. • 7 years old female child
• complaints of weight gain, puffiness of face,
rashes on face and body
• failure to gain height and hypertension since
1 year.
• Child also had few episodes of seizures (?
Hypertensive encephalopathy)

36. • Q. What is the definition of Hypertension in
Pediatric age group ?

39. • Q. When will you suspect Cushing’s
syndrome in a Child ?

40. • Short height + Increase of Weight

42. • Q. How is diagnosis of Cushing’s syndrome
Established in a child ?

43. • Similar to adults
• Only dose of Dexamethasone needs to be
adjusted

44. • Q. What is the dose of Dexamethasone used
for ONDST in children ?

45. – ONDST- 15 ug/kg
– LDDST - 30 ug/kg/day in 4 divided doses
– HDDST- 120 ug/kg/day in 4 divided doses
– For children > 40 kg- use same dose as adults

47. CASE #4

48. • 24 year old female
• c/o of headache and other non specific
complaints
• BP – 160/90 mm Hg
• Ix done – Aldosterone : Renin Ratio > 30:1

49. • Q. What is Primary Aldosteronism ?

50. • “PA is a group of disorders in which
aldosterone production is inappropriately
high for sodium status, relatively
autonomous of the major regulators of
secretion (angiotensin II, plasma potassium
concentration), and nonsuppressible by
sodium loading”

51. • Also called Conn’s syndrome

53. • Q. What are the causes of Primary
Aldosteronism ?

54. 1. Aldosterone production Adenoma (APA)
2. Bilateral Idiopathic adrenal hyperplasia (IHA)
3. Familial hyperaldosternism- type I- Glucocorticoid
remedible hypertension
4. Familal hyperaldosterone type II- mutations
producting familial APA / IHA
5. FHA type III- KCNJ5 mutation
6. Unilateral adrenal hyperplasia
7. Ectopic aldosterone producing tumor
8. Aldosterone producing carcinoma

55. • Q. How common is Primary Aldosteronism ?

56. • More common than you think !
• 5-10% of Hypertensive patients may have
Primary Aldosteronism !

57. • Q. Why is primary aldosteronism important?

58. • Higher CV morbidity and mortality compared
to other hypertensive patients of same age
and sex

59. • Q. Which patients should be tested for
Primary Aldosteronism ?

60. Endo Society guidelines
1. Sustained blood pressure (BP) above 150/100 mm Hg on each of
three measurements obtained on different days,
2. Hypertension (BP 140/90 mm Hg) resistant to three
conventional antihypertensive drugs (including a diuretic),
3. Controlled BP (140/90 mm Hg) on four or more antihypertensive
drugs;
4. Hypertension and spontaneous or diuretic-induced hypokalemia
5. Hypertension and adrenal incidentaloma
6. Hypertension and sleep apnea
7. Hypertension and a family
8. History of early onset hypertension or cerebrovascular accident
at a young age (40 years);
9. All hypertensive first-degree relatives of patients with PA.

61. • Q. What is classical triad of PA ?

62. 1. Hypertension
2.Hypokalemia
3.Metabolic alkalosis
•However most patients donot have all the
features of this triad

63. • Q. Do all patients with PA have hypokalemia
?

64. • This is a common mistake
• Infact Hypokalemia is only present in 10-30%
cases of Primary aldosteronism

65. • Q. What are the 3 steps in diagnosis of PA ?

66. • Case detection  Case confirmation 
Subtype classification

67. • Q. What is the screening test for PA ?

68. • Aldosterone- Renin ratio (ARR)

69. • Q. Which Drugs need to be stopped before
testing for ARR and for how long ?

70. Stop for 4 weeks
1. Spironolactone, eplerenone, amiloride, and
triamterene
2. Potassium-wasting diuretics
3. Products derived from licorice root (eg,
confectionary licorice, chewing tobacco)

71. Stop for 2 weeks
1. Beta Adrenergic blockers
2. Central alpa-2 agonists (eg, clonidine, alpa-
methyldopa)
3. nonsteroidal anti-inflammatory drugs
4. Angiotensin-converting enzyme inhibitors
5. angiotensin receptor blockers
6. renin inhibitors
7. dihydropyridine
8. calcium channel antagonists

72. • Q. Which antihypertensives to use during the
interim period to control the BP ?

74. • Q. Can OC Pills be continued ?

75. • OC pills need to be stopped if Direct Renin
concentration is measured
• No need to stop if PRA is measured

76. • Q. What other precaution need to be taken ?

77. 1. Correct the hypokalemia if present before
testing
2. Liberal salt intake for 1-2 weeks before
testing

78. • Q. What is the protocol for testing ?

80. • Q. What is the screening cutoff to consider
PA based on Aldosterone- Renin ratio ?

82. • Q. A patient has Aldosterone value of 3 ng/dl
and PRA of 0.1 ng/ml/hr, the ratio is 30:1 ,
does he have primary aldosteronism ?

83. • No
• This is the catch
• To call it a Primary aldosteronism, the PAC
should be >15 ng/dl and PRA <1 ng/ml/hr

84. • Q. Give the DD of secondary causes of
hypertension based on PAC / PRA values ?

86. • Q. What is done once diagnosis of Primary
Aldosteronism is established ?

89. CASE #5

90. • 39 year old female
• Presented with severe headache, vomiting
• BP was 180/110 mm Hg in emergency
• MRI Brain- was normal
• Emergent management of hypertension done and
then discharged with Anti Hypertensives
• BP- 110/70 mm Hg on OPD follow up
• Again after 15 days- presented to emergency with
Similar episode
• BP – 170/110 , ECG- Sinus tachycardia with HR of 110
beats per minute

91. • Admitted and start on Sodium Nitroprusside
under Cardiology
• Reference done to Nephrology, Neurology
and Endocrinology !
• Our Routine protocol detected high urinary
metanephrine
• MRI was suggestive of Large
Pheochromocytoma

93. • Q. In Which patients would you Consider
Pheochromocytoma ?

94. • The classic triad of headache, sweating, and tachycardia
• Hyperadrenergic spells (eg, self-limited episodes of nonexertional
palpitations, diaphoresis, headache, tremor, or pallor).
• Onset of hypertension at a young age (eg, <20 years), resistant
hypertension, or hypertension with new onset or atypical
diabetes mellitus (eg, new onset of apparent type 2 diabetes in a
slender person).
• A familial syndrome that predisposes to catecholamine-secreting
tumors (eg, multiple endocrine neoplasia type 2 [MEN2],
neurofibromatosis type 1 [NF1], or von Hippel-Lindau [VHL]).
• A family history of pheochromocytoma.
• Adrenal incidentaloma with or without hypertension.
• Pressor response during anesthesia, surgery, or angiography.
• Idiopathic dilated cardiomyopathy.
• A history of gastric stromal tumor or pulmonary chondromas
(Carney triad).

95. • Q. How will you Diagnose
Pheochromocytoma ?

96. 1. Urinary Metanephrine, Normetanephrine
and Dopamine
2. Plasma Metanephrine and
Normetanephrine

97. • Q. What is the role of VMA ?

98. • VMA has low sensitivity in Detection of
Pheochromocytoma
• Though it has good specificity

99. • Q. Which drugs can potentially cause false
elevation of Catecholamine ? How long are
they stopped before testing ?

100. 1. TCA- most notorious
2. SSRI
3. Amphetamine
4. Cough and cold medications

102. • Q. What food substances need to be avoided
and for how long ?

103. • Nuts
• Caffeine
• Chocolate
• Bananas
• Alcohol
• Vanilla
For 3 days prior to testing

104. • Q. What is the procedure for Collection of
tests for Metanephrine and
Normetanephrine ?

105. 1. Discard the first urine of the day
2. Start collection from next urine sample
onwards
3. Collect urine with appropriate volume of
50% HCl to maintain pH between 1–2.
(Generally container provided by lab)
4. Urine sample is kept in refrigerator in
between collection
5. Shipped refrigerated and frozen

106. • Q. How is plasma metanephrine test done ?

107. • Indwelling catheter in place
• Patient has overnight fast
• Patient supine for 30 min
• Sample is taken

108. • Q. Describe the further steps in evaluation of
Pheochromocytoma ?

110. FINALLY SOME IMPORTANT
PEARLS

111. • Drugs and ‘Complimentary alternative
Medicine’ intake

113. Other important history points
• Hypertension before age of 21 years and Family
history of Cerebral hemorrhage before age 40
years  GLUCOCORTICOID REMEDIABLE
HYPERTENSION (FAMILIAL
HYPERALDOSTERONISM TYPE 1)
• Obstructive Sleep Apnea- STOP BANG
questionnaire
• OC Pill use  OC pills can cause an increase in
BP (though increase is mild)

114. DON’T FORGET
• Palpate all four limb pulses and blood
pressure – Why ?
• Fundus Examination
• Auscultation for abdominal bruit for Renal
artery stenosis (Only 40% sensitivity but 99%
specificity)

115. TAKE HOME MESSAGE

116. Secondary Cause of
hypertension should be
considered in Resistant
hypertension and young
hypertensives

117. •Proximal Muscle
weakness
•Violaceous striae
•Facial flushing
Are high discriminant signs
for Cushing’s syndrome

118. Short height + Increase
weight – think of
Cushing’s in Young
children

119. Primary Aldosteronism is
more common than you
think

120. Urinary VMA is now
outdated test for
diagnosis of
Pheochromocytoma

121. THANK YOU !
DR. OM J LAKHANI
MD, DNB (ENDOCRINE)
CONSULTANT ENDOCRINOLOGIST
ZYDUS HOSPITAL, AHMEDABAD