Transcript Idiopathic Addison`s Disease

Idiopathic Addison’s Disease
with Premature Ovarian Failure
高雄榮民總醫院 皮膚科
賴名耀
宗天一
Case Report
 A 47 year-old female, menopausea for 8 years.
 Chief Complaints
 Hyperpigmentation
over face, trunk and four limbs
since 8 months ago.
 General malaise, palpitation, nausea, poor appetite,
dizziness, drowsiness, occasional itching,
mild body weight loss (62kg  57kg).
 Gestation History
G?P3, no menses since 39 years old
 Early menopause

 Drug History
 Denied drug taken before this episode
 Dietary supplement taken once at 7 months ago
 Family History
 Non-contributory
 Vital Sign
 BP:
126/72 mmHg
 PR: 62/min
 RR: 18/min
 BT: 36.3oC
 Skin Findings
Generalized brown-blackish, occasionally
pruritic hyperpigmentation over scalp, face,
neck, trunk, four limbs and creases of palms
and soles.
 Several black-bluish asymptomatic macules
over oral mucosa.
 Longitudinal brownish hyperpigmentation over
fingernails and toenails.

 Laboratory
Findings
 CBC&DC-- WBC:4210 ; S/L/M/E: 45/47/6/2 ; HgB:12.1
 Urine routine and stool routine: negative finding
 Electrolyte : Na+/K+: 142.0/4.0 ; Bun/Cr: 9.0/0.8
 TG:361.0 ; Cholesterol:125
 ANA: (-) ; RA factor : 61.6 IU/mL (< 30, )
 ATA: 21 nU/ml (<220) ; AMiA: 45 nU/ml (<100)
 TIBC: 258 ug/dl (206-380) ; Ferritin:153 ng/ml (9-90, )
 Urine TB culture and AFS : negative
 Hormone
Laboratory Data
 Cortisol (AM): 3.72 ng/dl (9-23, )
 Cortisol (PM): 2.70 ng/dl (7-13, )
 Aldosterone: < 25.00 pg/ml (37.5-240,  )
 ACTH: >1250 pg/ml (0-46,  )
 DHEA-S(dehydroepiandrosterone, serum):
< 0.10 u mol/L (F:1.08-10.7, )
 E2: 22 pg/ml (post-M.P.: <20-41)
 FSH: 54.24 mIU/ml (post-M.P.:20-138)
 LH: 40.97 pg/ml (post-M.P.: 15-62)
 Image Findings
 Skull and chest x ray: negative finding.
 CT scan of adrenal glands: normal appearance of
the adrenal glands without significant tumor mass
lesion, calcification or hemorrhage.
 Pathological Findings
 Hyperpigmentation featuring increased melanin
pigment in basal cells.
 Diagnosis
Idiopathic Addison’s disease with premature
ovarian failure
 Treatment
Oral intake cortisone 25 mg twice a day
Discussion
Addison’s Disease
 Incidence
 Rare
(1 in 4500-6250)
 Age:
any age, frequently at 30~40 year-old

Sexe: F:M=1.08:1 ~ 3.74:1
 Etiology
 Autoimmune
disease (65% - 84%)

Infection (30%)

Metastases (rare)

Others: hemorrhage, drugs, infiltrated diseases
 Premature
 A syndrome
Ovarian Failure
characterized by menopause before the
age of 40 years
 Incidence: 0.9%
 Etiology: chromosomal, genetic, enzynatic, infectious
iatrogenics, and autoimmune
 The first sign of autoimmune endocrine disease.
 2-10% of the autoimmune POF patients is associated
with Addison’s disease
 POF may be noted before Addison’s disease 8-14 years
 Clinical Symptoms of Addison’s Disease
 Weakness (99%)
 Pigmentation of skin (98%)
 Pigmentation of mucous membranes(82%)
 Weight loss (97%)
 Anorexia, nausea and vomiting (90%)
 Hypotension (< 110/70) (87%)
 Abdominal pain (34%)
 Salt craving (22%)
 Diarrhea (20%)
 Constipation(19%)
 Cutaneous Manifestations of
Addison’s Disease
 Darker in sun-exposed areas.
 Darkening also occurs in areas of trauma, recent scars,
and points of pressure and friction.
 Skin in sexual areas become darker.
 Hair darken and longitudinal pigmented bands appear
on the nail.
 Pigmentation appears on mucosal surface, especially
the buccal mucosa, gums and tongue.
 Histopathology of Addison’s Disease
 The findings simulate the normal findings in patients
with natural dark skin.
 Increased amounts of melanin are seen in the basal
keratinocytes and often in the keratinocytes in the
upper spinous layer.
 The number of melanocytes is not increased ; variable
numbers of melanophages may be seen in the papillary
dermis.
 Not diagnostic.
 Laboratory Findings:
 Early Phase:
Basal steroid output is normal
 Increase dose not occur in response to stress


More advanced Phase:
Na+, Cl-, HCO3- ---  ; K+ --- 
 Extracellular fluid volume: 
 Cortisol and Aldosterone are subnormal and fail to
increase following ACTH administration.
 EKG: nonspecific changes.
 Normocytic anemia, relative lymphocytosis and
usually a moderate eosinophilia.

 Diagnosis
 ACTH stimulation testing: To assay the adrenal
reserve capacity for steroid production.
 Plasma cortisol: 
 Plasma aldosterone: 
 Plasma ACTH and associated peptides
(-lipotropin) : 
 The Autoimmunity
 Adrenal cytoplasmatic antibodies (Cy-Ad-Abs);
Steroid-cell antibodies (St-C-Abs)
Prevalence of steroid-cell antibodies (St-C-Abs) in
patients and controls
Ovarian failure
Unselected infertility/amenorrhea
Without autoimmune thyroid disease or type 1 diabetes
With Addison's disease-primary amenorrhea
-secondary amenorrhea
Addison's disease (without ovarian failure)
Isolated cases
With hypoparathyroidism/candidiasis (type I PGAS)
With autoimmune thyroid disease (type II PGAS)
Healthy controls
<1%
5-10%
100%
60%
10-20%
60-80%
25-40%
<1%
 Addison’s Disease with
Premature Ovarian Failure
 Almost certainly an endocrine autoimmune disorder
 Reasons supported:
The presence of autoantibodies to steroid-producing
cells in the patients
 The characterization of shared autoantigens between
adrenal and ovarian steroid-producing cells
 Lymphoplasmacellular infiltrate particularly around
steroid-producing cells
 The existence of an animal model for the syndrome

 Differential Diagnosis of
Skin Hyperpigmentation
 Nelson‘s syndrome
 Hyperthyroidism
 HIV infection
 Siemerling-Cruezfeldt disease
 Hemochromatosis
 Universal acquired melanosis - the carbon baby
 POEMS syndrome
 Whipple’s intestinal lipodystrophy
 Porphyria cutanea tarda
 Hyperpigmentation in vitamin B12 deficiency
 Progressive systemic sclerosis
Treatment of Addison’s Disease

Replacement therapy

Cortisol 25 - 37.5 mg in divided dose
+ Fludrocortisone 0.05 - 0.1 mg per day.

Prednisolone 7.5 mg in divided dose.
Thank You