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Prof. Tariq Waseem
ADRENAL DISORDERS - 3
Prof. Tariq Waseem
Prof. Tariq Waseem
CASE SCENARIO:1 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
ADRENAL MEDULLA
Prof. Tariq Waseem
EXAMINATION 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
LAB INVESTIGATION SHOWED:
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
PHEOCHROMOCYTOMA 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
PHEOCHROMOCYTOMA 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
PHEO: SIGNS & SYMPTOMS 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
BIOCHEMICAL TESTING Plasma Fractionated free metanephrine
levels Urinary fractionated metanephrines and
metabolites Serum chromogranin A Clonidine suppression test Urinary VMA levels Additional tests include…
erythrocytosis,leukocytosis,hyperglycemia,hypercalcemia,sometimes raised ESR
Prof. Tariq Waseem
FACTORS AFFECTING TEST RESULTS:
Physical or emotional stress Sleep apnea Drugs….MAO inhibitors, TCA’s, beta
blockers, amphetamine, levodopa, methyldopa, labetalol,buspirone, phenoxybenzamine
Prof. Tariq Waseem
IMAGING
Silent 8 cm pheo
Prof. Tariq Waseem
IMAGING
CT/ MRI abdomen Nuclear imaging….123 meta-
iodobenzyl-Guanidine PET scanning…18FDG-PET Somatostatin receptor imaging…111in-
labeled octreotide
Prof. Tariq Waseem
TREATMENT:
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
INTERVENTIONS-PRE-OP 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
PREOP PREPERATION REGIMENS Combined + blockade
Phenoxybenzamine Selective 1-blocker (ex. Prazosin) Propanolol
Metyrosine Calcium Channel Blocker (CCB)
Nicardipine
Prof. Tariq Waseem
DURING SURGERYGIVE REGITINE AND NIPRIDE TO PREVENT HYPERTENSIVE CRISIS
Prof. Tariq Waseem
POSTOP 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
COMPLICATIONS. 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
PHEO: UNRESECTABLE, MALIGNANT -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
PHEO & PREGNANCY 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
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.
CASE SCENARIO:
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.
CONGENITAL ADRENAL HYPERPLASIA:
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.
CONGENITAL ADRENAL HYPERPLASIA:
Cholesterol
Pregnenolone
17-Hydroxy-pregnenalone
17-Hydroxy-progesterone
11-Deoxycortisol
Cortisol
desmolase
17-a-hydroxylase
11-b-hydroxylase
21-hydroxylase
3-b-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:
CLASSICAL 21-HYDROXYLASE DEFICIENCYPATHOPHYSIOLOGY
Glucocorticoid
Cholesterol(mitochondrial)
Pregnenolone
17OH-Pregnenolo
ne
17OH-Progesterone
Cortisol
Progesterone
11-deoxycorticosteron
e
Aldosterone
Mineralocorticoid
P-45021
Dehydroepiandrosterone
Androstenedione
(Testosterone)
Oestradiol DHT
Androgen
ACTH_
++
11-deoxycortisol
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,
CLINICAL FEATURES:
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
INVESTIGATIONS:
MANAGEMENT :
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
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)
MANAGEMENT :
Corrective surgery to genitalia
Genetic counselling & psychological support
MANAGEMENT :
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.
CASE SCENARIO:3
B.P 160/100 Pulse…86/ min, regular Respiratory rate..18/min No peripheral edema. Systemic examination was
unremarkable
PHYSICAL
CBC , LFT’S, RFT’S…Normal Serum potassium..2.1meq/L, serum
sodium..156meq/l Urinary postassium..> 32mmol/day
What’s the diagnosis ?
INVESTIGATIONS
Primary Hyperaldosteronism
Conn’s Syndrome
HYPERALDOSTERONISM
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.
HYPERALDOSTERONISM
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.
HYPERALDOSTERONISM:
Frequent urination Increased thirst Weakness and fatigue Headache Muscle cramps Tingling in fingers Transient paralysis Palpitations Hypertension
SYMPTOMS
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.
INVESTIGATIONS:
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
INVESTIGATIONS:
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.
TREATMENT:
Bilateral adrenal hyperplasia..best treated with spironolactone or eplerenone.
Secondary hyperaldosternism…ACE’s and ARB’s, spironolactone.
MANAGEMENT :
Prof. Tariq Waseem
THANK YOUQuestions?