A 34-year-old male presented with body aches, muscle weakness, numbness, and tingling in the limbs for 5 days. He also had polyuria, polydipsia, headaches and palpitations. He was found to have hypokalemia (potassium 2.1) and hypernatremia (sodium 156). He was diagnosed with primary hyperaldosteronism or Conn's syndrome, which causes hypokalemia and hypertension due to excessive aldosterone secretion. Treatment depends on the cause, including surgery for unilateral adenomas or medication with aldosterone antagonists for bilateral adrenal hyperplasia.

1. Prof. Tariq Waseem
Prof. Tariq Waseem

3.  A 22 years old male presents with c/o severe
headache off & on, palpitations and sweating
while carrying out his daily activities.
 He also complains of having a sense of
impending doom and generalized weakness
of his body along with trembling of his hands
 His co-workers also noticed marked blushing
of his face during such episodes.
 He was diagnosed HTN one year ago and is
using four antihpertensive drugs but his BP is
rarely on target.
Prof. Tariq Waseem

4. Prof. Tariq Waseem

5.  On physical examination:
 BP= 210/140
 Pulse…92/min regular
 Temp…98.6 F
 Other positive findings include:
 Pallor…+ve
 Tremors…present
 Systemic examination was unremarkable
Prof. Tariq Waseem

6.  CBC.showing Hb..15g/dl
 TLC…18000
 Serum Na+…139meq/l
 Random blood glucose..200 mg/dl
 Normal T3, T4, TSH
 Normal ECG and echo
Prof. Tariq Waseem

7.  Rare but fatal catecholamines producing
tumor
 Incidence: 2-8/million people/year
 Account for 5% of adrenal incidentaloma
 Rule of 10s:
 10% extra-adrenal, 10% bilateral, 10% familial,
10% malignant
 Aside from catecholamines, it can also
secrete dopamine, ACTH, PTH, calcitonin,
VIP
Prof. Tariq Waseem

8.  0.01-0.1% of HTN population
 Found in 0.5% of those screened
 M = F
 3rd to 5th decades of life
 Rare, investigate only if clinically
suspicion:
 Signs or Symptoms
 Severe HTN, HTN crisis
 Refractory HTN (> 3 drugs)
 HTN present @ age < 20 or > 50 ?
 Adrenal lesion found on imaging (ex. Incidentaloma)
Prof. Tariq Waseem

9.  The five P’s:
 Pressure (HTN) 90%
 Pain (Headache) 80%
 Perspiration 71%
 Palpitation 64%
 Pallor 42%
 Paroxysms
 The Classical Triad:
 Pain (Headache), Perspiration, Palpitations
 Lack of all 3 virtually excluded diagnosis of pheo in a
series of > 21,0000 patients
Prof. Tariq Waseem

10.  Plasma Fractionated free metanephrine
levels
 Urinary fractionated metanephrines and
metabolites
 Serum chromogranin A
 Clonidine suppression test
 Urinary VMA levels
 Additional tests
include…erythrocytosis,leukocytosis,hypergly
cemia,hypercalcemia,sometimes raised ESR
Prof. Tariq Waseem

11.  Physical or emotional stress
 Sleep apnea
 Drugs….MAO inhibitors, TCA’s, beta blockers,
amphetamine, levodopa, methyldopa,
labetalol,buspirone, phenoxybenzamine
Prof. Tariq Waseem

12. Prof. Tariq Waseem
Silent 8 cm pheo

13.  CT/ MRI abdomen
 Nuclear imaging….123 meta-iodobenzyl-
Guanidine
 PET scanning…18FDG-PET
 Somatostatin receptor imaging…111in-
labeled octreotide
Prof. Tariq Waseem

14.  SURGERY…treatment of choice for all
pheochromocytomas ( laproscopic
adrenalectomy, open laprotomy)
 Careful pre-operative management to control
blood pressure, correct fluid volume and
prevent intra-operative hypertensive crises
 MEDICATION therapy….for preop
management, acute hypertensive crises and
as a primary therapy for metastatic
pheochromocytoma.
Prof. Tariq Waseem

15.  Adrenergic blocking agents
 Minipress to BP
 Beta blocking agents
 Inderal to Heart Rate, BP & force of contraction
 Diet
 High in vitamin, Mineral, Calorie, No Caffeine
 Sedatives
Prof. Tariq Waseem

16.  Combined  +  blockade
 Phenoxybenzamine
 Selective 1-blocker (ex. Prazosin)
 Propanolol
 Metyrosine
 Calcium Channel Blocker (CCB)
 Nicardipine
Prof. Tariq Waseem

17. GIVE REGITINE AND NIPRIDE
TO PREVENT HYPERTENSIVE
CRISIS
Prof. Tariq Waseem

18.  Most cases can stop all BP meds postop
 Postop hypotension: IV crystalloid
 HTN free: 5 years 74% 10 years 45%
 24h urine collection 2 wk postop
 Surveillance:
 24h urine collections q1y for at least 10y
 Lifelong f/up
Prof. Tariq Waseem

19.  All the complications of severe hypertension
 Catecholamine induced cardiomyopathy
 Severe heart failure and cardiovascular
collapse
 Sudden death due to cardiac arrhythmias
 ARDS
 Hypertensive crises with sudden blindness
and CVA’s…not uncommon
Prof. Tariq Waseem

20.  -blockade
 Selective 1-blockers (Prazosin, Terazosin, Doxazosin)
1st line as less side-effects
 Phenoxybenzamine: more complete -blockade
 -blocker
 CCB, ACE-I, etc.
 Nuclear Medicine Rx:
 Hi dose 131I-MIBG or 111indium-octreotide depending on
MIBG scan or octreoscan pick-up
 Sensitize tumor with Carboplatin + 5-FU
Prof. Tariq Waseem

21.  Diagnosis with 24h urine collections and
MRI
 No stimulation tests, no MIBG if pregnant
 1st & 2nd trimester (< 24 weeks):
 Phenoxybenzamine + blocker prep
 Resect tumor ASAP laprascopically
 3rd trimester:
 Phenoxybenzamine + blocker prep
 When fetus large enough: cesarian section followed by
tumor resection
Prof. Tariq Waseem

23.  A 16 yr old girl was brought to medical OPD
with C/O increased facial hair and acne. Her
mother is concerned about delayed menarche
and not having a smart feminine figure. On her
last visit to physician she was told to watch her
BP which was recorded 140/95 mmHg.
 On examination, pt. is having male type hair
pattern along with ambiguous genitalia.

24.  Congenital adrenal hyperplasia (CAH) is a
group of inherited autosomal-recessive
disorders in which a genetic defect results in
the deficiency of an enzyme essential for
synthesis of cortisol and, at times,
aldosterone.

25.  Reduced cortisol secretion and resulting absence of
feedback pituitary inhibition increases ACTH to
maintain adequate cortisol causing adrenal
hyperplasia.
 There are several forms of CAH, the most common of
which is 21-hydroxylase (21-OH) deficiency, occurring
in over 90% of all cases.

26. Cholesterol
Pregnenolone
17-Hydroxy-
pregnenalone
17-Hydroxy-
progesterone
11-Deoxycortisol
Cortisol
desmolase
17--hydroxylase
11--hydroxylase
21-hydroxylase
3--OH-
dehydrogenase
Androgens
Ambiguous, no androgens, salt-
wasting
Ambiguous, low androgens,
hypertension
Virilized, high androgens,
lethal
Virilized, high androgens, salt-
wasting
Virilized, high androgens,
hypertension
HGSS: Carey: Figure 5.2 Genitalia, androgen level, medical symptomKey:

27. Glucocorticoi
d
Cholesterol
(mitochondrial)
Pregnenolone
17OH-
Pregnenolone
17OH-
Progesterone
Cortisol
Progesterone
11-
deoxycorticosterone
Aldosterone
Mineralocorticoi
d
P-45021
Dehydroepiandrosterone
Androstenedione
(Testosterone
)
Oestradiol DHT
Androgen
ACTH
_
++
11-
deoxycortisol

29.  If severe, CAH presents at birth with sexual
ambiguity or adrenal failure ( collapse,
hypotension, hypoglycemia) sometimes with a
salt losing state( hypotension, hyponatremia).
 In females, clitoral hypertrophy, urogenital
abnormalities, and albioscrotal fusion are
common but syndrome may be unrecognized.
Milder cases present in adult life only with
primary amenorrhea.
 In males. Precocious puberty with hirsutism is
a later presentation,

30.  A profile of adrenocortical hormones is measured
before and 1hr after ACTH administration.
 Basal ACTH levels…are raised
 17-hydroxyprogesterone levels…are increased
 Urinary 17-ketosteroids are increased
 Androstenedione levels…are raised

31. Glucocorticoid replacement / Androgen Suppression
 Adults: usually dexamethasone, larger dose at bed-
time to suppress ACTH
 Beware of over-replacement and monitor :
17--progesterone (testosterone, cortisol, ACTH etc)
growth, bone age, BP, U&E, skin; osteoporosis scans
in adults

32. Correction of salt-wasting
 9-a-fludrocortisone 100-400mcg/day (long-
acting)
 Sodium chloride supplements until able to select
saltier foods
 Monitor BP, U&E, oedema (renin)

33. Corrective surgery to genitalia
Genetic counselling & psychological support

35.  A 34 yr old male presents in ER with C/O body
aches, episodic muscle weakness, numbness
and tingling of the limbs for last 5 days.
Symptoms worsened over 2 days leading to
severe muscle spasms.
 He also has polyuria and polydipsia especially
at night. He has frequent episodic headache
and Palpitation.
 He was diagnosed HTN last year and is on Beta
Blockers with poor control.

36.  B.P 160/100
 Pulse…86/ min, regular
 Respiratory rate..18/min
 No peripheral edema.
 Systemic examination was unremarkable

37.  CBC , LFT’S, RFT’S…Normal
 Serum potassium..2.1meq/L, serum
sodium..156meq/l
 Urinary postassium..> 32mmol/day
 What’s the diagnosis ?

38.  Primary Hyperaldosteronism
 Conn’s Syndrome

39.  Excessive secretion of aldosterone causes
 Increased Sodium reabsorbtion,
 Increased loss of potassium
 Increased loss hydrogen ions
 Hypokalemia and Hypertension.
 Peak incidence between 30-60yrs of age.

40.  May be primary ( autonomous) as in primary
adrenal hyperplasia, adrenal adenoma,
carcinoma
 Secondary hyperaldosteronism…associated
with renovascular hypertension, cirrhosis,
rennin producing tumours, pregnancy.
 Testing for primary hyperaldosteronism should
be done for all hypertensive patients with
hypokalemia.

41.  Frequent urination
 Increased thirst
 Weakness and fatigue
 Headache
 Muscle cramps
 Tingling in fingers
 Transient paralysis
 Palpitations
 Hypertension

42.  Hypokalemia ( Without Diuretic therapy)
 Urinary potassium loss..>30mmol/day
 Plasma aldosterone:rennin ratio
(ARR)…increased
 Elevated plasma aldosterone level (PA…that
are not suppressed with 0.9% saline ( 2L over
4hrs) or fludrocortisone administration.

43.  Suppressed plasma rennin activity
 18-hydroxycorticosterone level..>100ng/dl seen in
adrenal neoplasms.
 Adrenal vein sampling..to differentiate unilateral or
bilateral aldosteronism
 Posture stimulation test
 Imaging…CT abdomen

44.  Control of blood pressure.
 Conn’s syndrome(adenoma ), unilateral
aldosterone secreting adrenal tumours…treated
by laproscopic adrenalectomy though long term
therapy with spironolactone ( aldosterone
antagonist) or eplerenone is an option.

45.  Bilateral adrenal hyperplasia..best treated with
spironolactone or eplerenone.
 Secondary hyperaldosternism…ACE’s and ARB’s,
spironolactone.

47. Questions?
Prof. Tariq Waseem