This patient presented with multiple symptoms including loose motions, blisters, cough, shortness of breath, abdominal fullness, and limb swelling. Laboratory tests found hypothyroidism, hypokalemia, anemia, and leukocytosis. Sputum culture grew Klebsiella pneumoniae and Acinetobacter species. The patient was diagnosed with Addison's disease, hypothyroidism, acute gastroenteritis caused by Giardia, iatrogenic Cushing's syndrome and pneumonia. The patient has a history of taking hydrocortisone, fludrocortisone, thyroxine, and prednisone for Addison's disease and hypothyroidism treatment, but developed Cushing's

1. Case Presentation 3
Dipesh Tamrakar
MSc. Clin. Biochemistry
1

2. Case history
• A 50 years old woman from Rautahat presented to TUTH with chief
complaints of :
• Multiple episodes of loose motions (6-7 episodes)
• 1 ½ mths back, multiple blisters seen
• Cough and insidious shortness of breath gradually progressive serous
sputum
• Interference with sleep and orthopnea (+)
• Abdominal fullness and limb swelling
2

3. History of:
• Increased weakness and low BP for 2 mths followed by frequent falls
• Hyperpigmented patches over right leg, chest and upper back for 2
mths
• Multiple subcutaneous swellings for 3 yrs and removed 1 yr back
• Whitish patches over tongue for 10 days causing difficulty eating and
increased dryness of tongue
• Diuretic intake for 8 days
• Hypovolemic shock 4 yrs back
3

4. General physical examination
• GC: conscious, oriented to time, place and person
• Ill-looking
• Negative for Pallor & icterus
• B/L limb swelling and fatigue
• BP: 90/60 mmHg,
• Pulse: 66 bpm
• Temp: 97.9 0F
• RR: 22/min
• SpO2: 90%
4

5. • Chest: Bronchial / Breath sounds
• Rt. Supraclavicular, interscapular, supra-mammary and mammary
(Cavitation on Rt. Upper Zone)
• Lt. suprascapular
• CVS: S1S2M0
• P/A: soft, non distended, non tender, no organomegaly
• CNS: grossly intact
5

6. Lab investigations ???
• CBC
• RFT
• LFT
• RBS
• URINE RE.ME
• STOOL RE.ME
• CXR
• SPUTUM CS GS
6

7. Test Result Reference Range Conversion factor
Glucose Random 5.2 3.8 – 7.8 mmol/L X18 = mg/dl
Urea 4.3 1.6 – 7.0 mmol/L X6 = mg/dl
Creatinine 76.0 40 – 110 mol/L X0.01131 = mg/dl
Na+ 136.0 135 - 146 mEq/L
K+ 3.6 3.5 - 5.2 mEq/L
HbA1c 7.6 4.5 – 6.0 %
Total Calcium 1.8 2.1 – 2.6 mmol/L X4 = mg/dl
Inorganic phosphorus 2.1 2.5 – 4.8 mg/dl
Magnesium 1.5 1.7 – 2.5 mg/dl
7

8. Test Result Reference Range
B. Total 6.0 3 – 21 g/L
B. Direct 2.0 0.1 – 5 g/L
Total Protein 67.0 60 - 80 g/L
Albumin 32.0 37 – 47 g/L
AG Ratio 0.9:1 1.2 – 1.5:1
SGOT 25.0 5 - 40 U/L
SGPT 31.0 5 - 45 U/L
Alkaline Phosphatase 359.0 <306.0 U/L
Gamma GT 50.0 <50.0 U/L
LDH 764.0 <460.0 U/L
CPK 48.0 <195.0 U/L
8

9. Test Result Reference Range
fT4 15.1 10.2 – 28.2 pmol/L
TSH 5.3 0.46 – 4.68 IU/ml
Cortisol Random
Cortisol 8 am
3.7
199.0
M: 4.46 – 22.7 g/dL
E: 1.7 – 14.1 g/dL
9

10. Test Result Reference Range
RBC 4.58 4.5 to 6.5 million/l
PCV 37.2 40 – 54 %
Hb 11.0 12.0-16.0 gm/dl
MCV 81.2 82.9 - 98 fL
MCH 24.0 27-33 pg
MCHC 29.6 33-36 %
Total leucocyte count 14,640 4000 - 11000/cu mm
Neutrophils 85 40-75 %
Lymphocytes 10 20-45 %
Monocytes 5 2-10 %
Eosinophils 0 0-5 %
Basophils 0 0-1 %
Platelets 3.64 1.5 – 4.5 lakhs /cu mm 10

11. Peripheral Blood Smear
• RBC: Normocytic Normochromic
• WBC: Leukocytosis with neutrophilia, no atypical or blast cells seen
• Platelets: Adequate in number
• No malarial or filarial parasites seen
11

12. Other investigations ???
12

13. Microbiology investigations
• Sputum sample:
• Gram’s Stain: presence of GPC and GNB
• AFB stain: No AFB seen but few fungal stains
• Culture: Klebsiella pneumonie and Acinetobacter sps
• Gene Xpert: Negative
• Stool RE/ME:
• Cyst of G. lamblia
• Urine RE/ME:
• NAD
13

14. ABDOMINAL USG
• LIVER, GALL BLADDER, CBD, SPLEEN, PANCREAS, KIDNEY, URINARY
BLADDER, PROSTATE: NORMALLY PRESENTED
• Impression: Fatty liver
ECG
• Sinus tachycardia
14

15. Supportive tests ……..
• Anti TPO antibody
• Thyroid scan
• SUPRESSION TESTS
• ACTH level
15

16. DIAGNOSIS
k/c/o - Addison’s Disease with Hypothyroidism (4 yrs ago)
Acute Gastro Enteritis (Giardiasis)
Iatrogenic:
Pneumonia (Klebsiella, Acinetobactor)
Cushing’s syndrome
Osteoporosis
L3 compression
16

17. Adrenal gland
Anatomy
• are orange-colored glands that sit on
top of the kidneys near the spine,
just underneath the last rib and
extending down about an inch.
• Supra-renal glands.
• Shape: pyramidal ( usually right
adrenal is pyramidal, whereas the
left is shaped more like a half moon)
• Size: 2- 3 cm wide, 4- 6 cm long, and
about 1 cm thick.
• Weight: 6-10 g.
17

18. THE ADRENAL CORTEX
•The cortex is divided into 3 regions:
•Zona Glomerulosa
•Zona Fasciculata
•Zona Reticularis
•These secrete different hormones that carry out
specific functions throughout body
•Hormones produced by the adrenal cortex are
referred to as corticosteroids.
•These comprise mineralocorticoids, glucocorticoids
and androgens.
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19. ADRENALS
Zona Reticularis
Sex steroids (androgens)
Zona Fasciculata
Glucocorticoids (Cortisol)
Glucose homeostasis
Zona Glomerulosa
Mineralocorticoids (Aldosterone)
Na+, K+ and water homeostasis
Medulla: “Catecholamines”
Epinephrine, Norepinephrine
CORTEX
19

20. ADDISON’S DISEASE
• Thomas Addison, 1st reported hypofunction of the adrenal cortex in
1855
• Primary adrenocortical deficiency causing combined
mineralocorticoid and glucocorticoid deficiency
• Rare disorder with a prevalence of only 4-11 cases per 100,000
• If untreated, adrenal insufficiency can be fetal
• “general languor and debility, feebleness of the heart’s action,
irritability of the stomach, and a peculiar change of the color of the
skin”-summarizes the dominant clinical features
• Advanced cases are usually easy to diagnose, but recognition of the
early phases can be a real challenge
20

21. Etiology and Pathogenesis
• Results from progressive destruction or dysfunction of the adrenals
which must involve >90% of the glands before adrenal insufficiency
appears
• In early series, tuberculosis was responsible for 70-90% cases but the
most frequent cause now is IDIOPATHIC atrophy and autoimmune
mechanism
• Autoimmune destruction exact mechanism still unknown but some
antibodies (like Ab against enzyme 21-hydroxylase) causes adrenal
insufficiency by blocking the binding of ACTH to its receptors
• Autoimmune polyendocrine syndrome (APS type 1 or 2) may also
involve thyroid and pancreas.
21

22. 22
Causes of Primary Adrenal Insufficiency
Endogenous causes
Autoimmune disease Sporadic
Addison’s Disease (APS type 1)
Hypoparathyroidism (APS type 2)
Inborn errors Congenital adrenal hyperplasia
ACTH resistance syndromes
Vascular disorders Intra-adrenal hemorrhage
Infections and anticoagulants
Glandular infiltration Neoplastic
Leukemia
Lymphoma

23. 23
Causes of Primary Adrenal Insufficiency
Exogenous causes
Infection Granulomatous disease
TB, HIV, Cytomegalovirus, Histoplamosis
Drugs Blockers of steroid synthesis:
ketoconazole,mitotane
Glucocorticoid Receptor blockers: RU-486
Abdominal Irradiation Bilateral adrenalectomy

24. Clinical Signs and Symptoms
24

25. 25

26. Laboratory findings & Diagnosis
• In early phase of gradual adrenal destruction, no demonstrable
abnormalities in the routine lab parameters
• Initially adrenal reserve is decreased
• In advanced stages of adrenal destruction, serum sodium, chloride
and bicarbonate levels are reduced
• The hyponatremia is due to both to loss of Na+ into urine ( due to
aldosterone deficiency) and to movement into the intracellular
compartment
• This extravascular Na+ loss depletes extracellular fluid volume and
accentuates hypotension
26

27. • The ECG may show nonspecific changes and the EEG exhibits a
generalized reduction and slowing
• There may be a normocytic anaemia, a relative lymphocytosis and
moderate eosinophilia
• Diagnosis of adrenal insufficiency should be made only with ACTH
stimulation testing to assess adrenal reserve capacity for steroid
production
• Measurement of basal ACTH and cortisol conc along with the ACTH
stimulation test is recommended if primary adrenal insufficiency is
suspected.
• Basal plasma ACTH conc >150 pg/ml and serum cortisol conc <10 g/dl
are diagnostic of adrenal insufficiency
• A subnormal cortisol response in the ACTH stimulation test supports
the diagnosis of primary adrenal insufficiency
27

28. 28

29. • The best screening test is the cortisol response 60 min after 250 ug of
Cosyntropin given IM/IV
• Cortisol levels should exceed 495 nmol/L (18 g/dL)
• If the response is abnormal, then primary and secondary adrenal
insufficiency can be distinguished by measuring aldosterone levels from
the same blood samples.
• In secondary adrenal insufficiency, the aldosterone increment will be
normal (5 ng/dL)
• Single-Dose Metyrapone Stimulation Test is not recommended in cases
of suspected Addison disease for fear that suppression of cortisol
production might precipitate an Addisonian crisis.
• That being said, patients with Addison disease have an inadequate rise in
11-desoxycortisol in response to metyrapone.
29

30. 30

31. 31

32. Differential Diagnosis
• Common signs and symptoms may be difficult to make diagnosis so it is
mandatory to perform ACTH stimulation testing to rule out adrenal
insufficiency, particularly before steroid treatment is begun
• Weight loss is useful in evaluating the significance of weakness and
malaise
• Racial pigmentation may be a problem but a recent and progressive
increase in pigmentation is usually reported by the patient with gradual
adrenal destruction
• Hyperpigmentation is usually absent when adrenal destruction is rapid,
as in bilateral adrenal hemorrhage
• When doubt exists, measurement of ACTH levels and testing of adrenal
reserve with the infusion of ACTH provide clear cut differentiation
32

33. • Diagnostic flowchart for evaluating patients with suspected adrenal insufficiency33

34. 34

35. Treatment
• Requires specific hormone replacement therapy
• It should correct both glucocorticoid and mineralocorticoid
deficiencies
• Hydrocortisone (cortisol) is the main stay of treatment
• Since the replacement dosage of hydrocortisone does not replace the
mineralocorticoid component of the adrenal hormones,
mineralocorticoid supplementation is usually needed: fludrocortisone
• The adequacy of mineralocorticoid therapy can be assessed by
measurement of BP and serum electrolytes
35

36. Iatrogenic Cushing’s Syndrome
• In 1912 Harvey Cushing 1st described the polyglandular syndrome
with pituitary involvement.
• Cushing’s syndrome is the result of autonomous, excessive
production of cortisol leading to classic symptoms characteristic of
this disorder
• Frequently the cause is iatrogenic; excessive exogenous steroid
therapy
• In the form of Cushing’s syndrome associated with primary adrenal
disease s/a adrenocortical adenoma, increased secretion of cortisol
suppresses both CRH synthesis and ACTH secretion
36

37. 37

38. 38

39. 39

40. Medications History of Case:
• On coysolone 5 mg and fludricort 100 mg
• 2 yrs back switched to:
• Hydrocort 200 mg and
• Methyl prednisolone 8 mg
• Thyronorm 50 ug
• Emsolone 20 mg
• Fossil 70 mg
• Fludricortisone 100mg
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42. THANK-YOU
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