ADRENAL DISORDERS

M Aron Pase, Dharma Lindarto

Div. Endokrinologi-Metabolik
Dep. Ilmu Penyakit Dalam FK USU/RSUP H Adam Malik
Medan
 Hypothalamus-Pituitary-Adrenal axis
Circadian regulation
Stress:
Physical stress
+ Emotional stress
Hypoglycemia
- Cold exposure
- Pain
CRH Cortisol
Adrenal cortex
+ -

ACTH +
Anterior lobe
of pituitary gland

CRH=corticothropin releasing hormone; ACTH=adrenocorticothropin hormone. Kirk LF. Am Fam Physician 2000
Cross section through the adrenal
gland cortex and medulla

salt

sugar

sex
Adrenocortical disorders
 Cushings Syndrome
Supraphysiologic glucocoticoid exposure
(excess cortisol)
Protein catabolic state
Liberation of amino acids by muscle
AA are transformed into glucose and glycogen and
then transformed into fat
The source of excess glucocorticoids may be
exogenous or endogenous
 Causes of Cushings Syndrome
ACTH Dependent (80%)
Cushings Disease (85%)
Primary excretion of ACTH from pituitary
Microadenoma, macroadenoma or corticotrophic hyperplasia
Basophilic or chromophobe
F>M (3:1)
Ectopic source (15%)
Produce ACTH or CRH
Small cell lung CA (most common), carcinoid tumors,
medullary thyroid, pancreas, ovarian,
pheochromocytoma, small-cell CA of prostate
 Causes of Cushings Syndrome
ACTH Independent
Exogenous steroid use (common)
PO or topical
Most common cause (overall)

Adrenal adenomas (10%)

Adrenal carcinoma (5%)
Most common cause in children
 Cause of Cushings Syndrome
Pseudo-Cushings disease
Mimic clinical signs and symptoms
Non-endocrine causes
Alcoholism
Major depression
Morbid obesity
Acute illness
 Cushings Syndrome
Symptoms and Sign Percent of Patients
Weight gain, round facies and 97
truncal obesity
Weakness 87
Hypertension 82
Hirsutism (in women) 80
Amenorrhea 77
Cutaneous striae 67
Ecchymoses 65
Osteoporosis Common
Hyperglycemia Common
 Hypercortisolism Cushing's syndrome
Moon face (round, red, and full)
Buffalo hump (a collection of fat between the shoulders)
Central obesity with protruding abdomen and thin extremities
Weight gain
Weakness
Backache
Headache
Acne or superficial skin infections
Thin skin with easy bruising
Thirst
Increased urination
Purple striations on the skin of the abdomen, thighs, and breasts
Mental changes
Impotence or cessation of menses
Facial hair growth
Cushing Syndrome
 Diagnosis of Cushings Syndrome
Clinical assessment
Screening tests :
Baseline glucocorticoids (a.m. and p.m. serum cortisol
levels, 24-hr urinary free cortisol excretion; 11 p.m.
Salivary cortisol)
Low dose dexamethasone suppression test or combined
low-dose dexamethasone-oCRH
Subtype diagnosis
Plasma ACTH concentration
Dynamic testing (oCRH stimulation test, metyrapon
stimulation test, high dose dexamethasone supression
test) all with limited utility or prescision
Directed computerized imaging (pituitary, adrenals, lungs,
etc)
Pituitary venous sampling for ACTH with CRH stimualtion
 Diagnosis of Cushings Syndrome
Screening tests
24 hour urinary cortisol (UFC)
RIA : 80-108g (221-298nmol)
Baseline 24-hour UFC measurements may be high : Carbamazepin, high
urine volume, severe illness, CS, alcoholism, depression, sleep apnea.
Late night plasma or salivary cortisol
A midnight sleeping serum cortisol concentration > 1.8g/dl (>50nmol/L)
is 100% sensitive in patients with Cushings syndrome.
Overnight 1-mg dexamethasone supression test (DST)
A failure to supress serum cortisol with 1-mg DST is positive screen and
should lead to confirmatory evaluations.
Causes for cortisol non-supression with the overnight 1-mg DST incl : CS,
patient error in taking, estrogen therapy, pregnancy, renal failure, stress,
drugs (anticonvulsants, rifampisin), obesity, psychiatric disorder
(depression, panic attacks)
 Diagnosis of Cushings Syndrome
Confirmatory tests for CS
When baseline 24-hour UFC is >300g (828 nmol) and the
clinical and the clinical picture is consisten with CS : no
additional confirmatory studies are needed.
2-day low dose DST
24-hour UFC < 300g : should confirmed with the low dose DST
(dexamethasone 0.5 mg, orally every 6 hours for 48 hours); 24-
hour urinary cortisol excretion > 20 g (55nmol) confirm diagnosis.
The low dose DST works best for those patients that carry of low
index of suspicion for CS.
Dexamethasone oCRH test
To correct false negative supression with DST (pituitary dependent
CS)
 Differential Subtype Evaluation Tests
Plasma ACTH concentration
ACTH dependent (normal to high levels of ACTH or ACTH independent
(low/undetectable ACTH)
IRMA assay : normal 10-60 pg/ml, plasma ACTH values are <5 pg/ml in adrenal
dependent disease, 10 to 200 pg/ml in pituitary-dependent disease, and 50 to
>200 pg/ml in ectopic ACTH syndrome
ACTH Dependent Disease
Pituitary MRI
Inferior petrosal venous sampling (IPSS) with CRH stimulation
Measure petrosal venous sinus ACTH level and correlate to plasma levels
The most important advanced in the past 2 decades for subtype evaluation of CS
IPSS does not diagnose Cushings syndrome
CRH stimulation test
High dose DST
Positron emission scanning: occult neuroendocrine and ather ACTH-secreting
tumors
No test is perfect for subtype evaluation of Cushings syndrome!
 Cushings Syndrome
Treatment program :
The resolution of hypercorticolism
The parellel treatmet of the complications of CS (e.g.
hypertension, osteoporosis, diabetes mellitus, mucle
rehabilitation)
Management of glucocorticoid withdrawal and hypothalamic
pituitary-adrenal (HPA) axis recovery
Treatment: Surgical
Cushings disease
Transphenoidal surgery (TSS)
The treatment choice
The longterm surgical cure rate for ACTH secreting microadenomas is
80-90%.
Transient post-op diabetes insipidus, adrenal insufficiency, CSF
rhinorrhea, meningitis
Tansphenoidal irradiation
If TSS is not curative.
High success rate in kids (80%)
Low success in adults (20%)
 Cushings Syndrome
Treatment: Surgical
Cushings disease
Bilateral adrenalectomy
If failed pituitary surgery
Life-long steroid replacement
Adrenal lesions/carcinoma
Removal of primary lesion
Survival based on underlying disease
Ectopic ACTH lesions
Remove lesion
Survival based on primary disease
May need bilateral adrenalectomy to control symptoms if primary
tumor unresectable
 Cushings Syndrome
Treatment: Medical
Used as prep for surgery or poor operative candidate
Metyrapone- inhibits conversion of deoxycortisol to cortisol
Aminoglutethimide-inhibits desmolase
Cholesterol to pregnenolone
Blocks synthesis of all 3 corticosteroids
Side effects: N/V, anorexia, lethargy
Ketoconazole- an imidazole that blocks cholesterol synthesis
Mitotane (O-P-DDD)-inhibits conversion to pregnenolone
Inhibits final step in cortisol synthesis
Destroys adrenocortical cells (spares glomerulosa cells)
 Cushings Disease
Increased Glucocorticoids
Etiology: Functional Cortical Adenoma or ACTH
secreting Pituitary Adenoma
Usually Young Adult Females
Clinical: Weight gain with fatty accumulation in
upper back (Buffalo Hump) and face (Moon
Facies); Delayed wound healing; Depression
Laboratory: Hypertension and High Blood Sugar
Dental: Poor Wound Healing; Risk of Adrenal
(STRESS) Crisis

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 Addisons Disease
Background: Thomas Addison first described the
clinical presentation of primary adrenocortical
insufficiency (Addison disease) in 1855 in his classic
paper, On the Constitutional and Local Effects of
Disease of the Supra-Renal Capsules.
Pathophysiology:
Addison disease is adrenocortical insufficiency due to the
destruction or dysfunction of the entire adrenal cortex.
It affects both glucocorticoid and mineralocorticoid
function.
The onset of disease usually occurs when 90% or more of
both adrenal cortices are dysfunctional or destroyed.
 Cortisol

Abdominal pain Gluconeogenesis Renal K Secretion ACTH

Anorexia Glucose uptake Renal Na secretion
Vomiting
Diarhea Hyperpigmentation

Fluid intake Hypoglycemia Hyperkalemia

Hyponatremia
dehydration

Hypotension
Hypovolemia

Renal perfusion Decreased Body Weight

BUN General Weakness
 Addisons Disease
Primary adrenal insufficiency
Causes
Infectious
TB most common cause in 3rd world countries
HIV, histoplasmosis, blastomycosis, coccidiomycosis
Autoimmune disorders anti-adrenal antibodies (most
cause common)
Medications ketoconazole, aminoglutethamide,
etomidate
Adrenal hemorrhage
Lymphoma, bilateral adrenal metastasis, Kaposis
sarcoma
Infiltrative amylodosis, sarcoidosis,
adrenoleukodystrophy
 Addisons Disease
Secondary adrenal insufficiency
Pituitary failure panhypopitutarism,
Sheehans syndrome (post-partum pituitary
injury)
Tertiary adrenal insufficiency
Adrenal suppression due to glucocorticoid use
Chronic suppression
Sudden cessation of replacement glucocorticoids
Inadequate increase during stress, trauma, surgery
 Primary Adrenal Insufficiency
Symptoms and sign Percent of
Patients
Weakness and fatigue 99
Hyperpigmentation 98
Unexplained weight loss 97
Anorexia, nausea, and vomiting 90
Hypotension (BP < 110/70 mmHg) 88
Hyponatremia 88
Hyperkalemia 64
 Primary Adrenal Insufficiency
A triphasic pattern :
Phase 1 : few/no symptoms, non spesific malaise,
pigmentation
Phase 2 : gradually worsening simptoms ; lethargy,
weight loss, increased pigmentation over exposed
areas, hypotension, anorexia, nausea, diarhoea, loss
axillary, pubic and body hair
Phase 3 : decompentation ; adrenal crisis,
 Primary versus secondary adrenal
insufficiency
Manifestations Primary Secondary
Hyperpigmentation Yes No
Pallor No Yes
Low Na Yes No
High K Yes No
Hypotension Yes No
Cortisol level Low Low
ACTH level High Low
Addisons Disease
 Addisons Disease

www-clinpharm.medschl.cam.ac.uk/.../addisons.jpg
 The End
Diabetic
Periodontal Abscess

Hyperthyroidism
Diabetic Angiopathy

Addisons Disease
Pigmentation
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