INTERESTING CASE OF
HEPATOMEGALY
PROF S.SUNDAR’S UNIT
Dr.A.NILAVAN PG
• 18 year old female was referred from GH for
evaluation of hepatomegaly
• H/o abdominal pain
• No h/o fever/ yellowish urine or eyes/ pruritis/clay
coloured stools
• No H/o joint pain or rash
• No H/o polyuria /polydipsia
• No h/o vomiting/hemetemesis/melena/loose stools
• No H/o weight loss/ loss of appetite
• No H/o cold or heat intolerance
• No H/o weakness /blurring of vision
• Past H/o
Not a k/c/o hypertension/DM / bronchial
asthma
No H/o blood transfusion in the past
• Personal H/o
Mixed diet
attained menarche at 17 yrs
cycles regular 3/28
• Family H/o
Non consanguinous marriage
One younger brother and sister- both normal
• General examination
Pt concious, oriented ,afebrile
no icterus pallor/ cyanosis/
clubbing/lymphadenopathy
no features of chronic liver disease
no KF ring
Alopecia+
Hyperpigmentation over forehead, around
eyebrows, tongue,palm,buccal
mucosa
BP: 90/70 mmhg
• Systemic examination
CVS: S1 ,S2 +
No murmur
RS : NVBS +
No added sounds
P/A : soft , firm liver palpable around4cm
below RCM, Liver span 20cm
No free fluid/ splenomegaly
CNS: NFND
INVESTIGATION
Hb 13.5g/dl
TC 6300 cells per cu. Mm
DC P 62 L34M4
ESR 30 mm/hr
PLATLET COUNT 240000 cell per cu.mm
HAEMATOCRIT 36
UREA 17mg/dl
CREATININE 0.7mg/dl
SODIUM 134 meq/l
POTTASIUM 5.6meq/ l
CHLORIDE 104 meq/l
CALCIUM 8.8mg/dl
PHOSPHORUS 4.1mg/dl
RBS(mg/dl) 356
CONT…
12/12/10 15/12/10 18/12/10 22/12/10
FBS (mg/dl) 440 301 192 148
PPBS( mg/dl) 546 361 355 172
Total bilirubin 0.77mg/dl
Direct bilirubin 0.32mg/dl
AST 441u/l
ALT 348u/l
SAP 230u/l
GGT 235u/l
PT 17sec
INR 1.7
• Urine routine
sugar: 3+
albumin: nil
deposits: 2-3 epithelial cells
Bile salts& Bile pigment : negative
ketones : negative
• 24 hrs urinary protein:120 mg
ECG : NSR, WNL
Xray chest pa view: normal study
Echo : normal study
USG abdomen : hepatomegaly, portal vein
normal size, spleen, pancreas normal
Fundus : normal
Slit lamp examination: normal
Viral markers : negative
HIV ,ELISA : Non reactive
UGI SCOPY : normal
PROVISIONAL DIAGNOSIS
• DM? type 1
• Autoimmune hepatitis
• Haemochromatitis
• Wilson s disease
FURTHER INVESTIGATIONS
• Serum iron -80micro g/dl
• Serum ferritin -200 ng /ml
• Serum transferrin – 320 mg/dl
• Total iron binding capacity- 300 micro g/dl
• ANA –negative
• Anti LKM-1 -negative
• AntiSLA –negative
• Serum ceruloplasmin- 25 mg/dl
• 24 hrs urinary copper- 30 microg/day
• T3 -60 ng/dl
• T4 free- 0.4ng/ml
• TSH -23micro Iu/ml
• TPO antibody- positive
• GAD antibody- positive
• Islet cell antibody- positive
• Anti mitochondrial antibody- negative
• Anti smooth muscle antibody -positive
• Serum ACTH-92pg/dl
• Serum cortisol-6microgram/dl. After cosyntropin
stimulation increased to 14 microgram/dl
FINAL DIAGNOSIS
Polyglandular autoimmune
syndrome type II (PGA-II)
TREATMENT
• INSULIN
• ELTROXIN
• FLUDROCORTISONE
• PREDNISONE
• UDCA
Polyglandular autoimmune syndrome
type II (PGA-II)
Most common of the immunoendocrinopathy syndromes.
Autoimmune Addison's disease
Thyroid autoimmune diseases
Type 1 diabetes mellitus
Primary hypogonadism, myasthenia gravis, and celiac
disease
The most frequent clinical combination association is
Addison's disease and Hashimoto's thyroiditis
Adulthood, usually around the third and fourth decade.
Middle-aged women
Associated with HLA-DR3 and/or HLA-DR4 haplotypes,
Pattern of inheritance is autosomal dominant with variable
penatrance.
Type 1 diabetes mellitus
Symptoms - Polyuria, polydipsia, polyphagia, unexplained weight
loss, intermittent blurred vision, and lethargy
Signs - Depend on the severity; consist of poor skin turgor,
orthostasis, and hypotension
Hashimoto's thyroiditis (chronic lymphocytic
thyroiditis)
Symptoms - cold intolerance, fatigue, somnolence, poor memory,
constipation, menorrhagia, myalgias, and hoarseness
Signs - Slow tendon reflexes, bradycardia, facial and periorbital
edema, dry skin and nonpitting edema, carpal tunnel syndromes,
deafness, and pericardial or pleural effusions
Seronegative arthritis
Graves disease
Symptoms - Heat intolerance, weight loss, weakness, palpitations,
oligomenorrhea, and anxiety
Signs - Brisk tendon reflexes, fine tremor, proximal weakness, stare and eyelid
lag, exophthalmos, atrial fibrillation, and sinus tachycardia
Addison's disease (primary adrenal
insufficiency)
Symptoms - Anorexia, nausea, vomiting, weight loss, weakness, and fatigue
Signs - Chronic hyperpigmentation of creases and scars, as well as orthostatic
hypotension
• Celiac disease
Weight loss, steatorrhea, bloating, cramping, and
malnutrition
• Pernicious anemia
Pallor, jaundice, ataxia, glossitis, impaired cognition,
impaired vibratory and position sense, and impaired cognition
• Other disorders associated with PGA-II
– Hypogonadism (usually autoimmune oophoritis)
and hypopituitarism
– Idiopathic thrombocytopenic purpura
– Myasthenia gravis
– Parkinson's disease
– Vitiligo
– Alopecia
DIFFERENTIAL DIAGNOSIS
• DiGeorge syndrome
• Kearns – Sayre syndrome
• Wolfram’s syndrome
• Cong . Rubella
• IPEX syndrome
Laboratory Studies
Serum autoantibodies screen
• 21-hydroxylase
• 17-hydroxylase
• Thyroid peroxidase (TPO)
• Thyroid-stimulating immunoglobulins (TSI)
• Glutamic acid decarboxylase and islet cells
• Antitissue transglutaminase antibodies
• Immunoglobulin-A (IgA) endomysial antibodies and
antigliadin antibodies.
• Parietal cell and anti-intrinsic factor antibodies
• Gonadotropins [FSH], [LH]) and appropriate sex hormones
(testosterone, estradiol)
• TSH, free thyroxine (T4), and free triiodothyronine (T3)
• Adrenocorticotropic hormone (ACTH) level and Cortrosyn-
stimulation test
• Plasma renin activity and serum electrolytes
• Calcium, phosphorus, magnesium, and albumin
• Fasting blood glucose
• Complete blood count (CBC) with mean cell volume (MCV) and
vitamin B-12 levels
Medical Care
• With the exception of celiac disease and Graves disease,
the mainstay of treatment is primarily hormonal
replacement therapy
• T4 therapy can precipitate adrenal crisis if adrenal
insufficieny is present. So before starting thyroid hormone
patient should be screened for adrenal insufficiency and if
present should be treated with glucocorticoids.
• A decreasing insulin requirement in patients with type 1
diabetes mellitus can be one of the earliest indications of
adrenal insufficiency or renal dysfunction. This can occur
before the development of hyperpigmentation or
electrolyte abnormalities.
• Hashimoto's thyroiditis (Hashimoto's disease)
– aim is to achieve euthyroidism.
– Thyroid-stimulating hormone (TSH) is used to assess the level of
euthyroidism. After 6 weeks of therapy, measure plasma TSH.
Adjust the dose in increments of 12-25 mcg at intervals of 6-8
weeks until TSH is normal. Thereafter, annual measurements
can be taken to ensure compliance and prevent overtreatment.
• Type 1 diabetes mellitus
– It requires lifelong treatment with exogenous insulin.
– A roughly estimated dose for otherwise healthy individuals is
approximately 0.6-1.2 U/kg/d (35-50 U/d in adults)
• Pernicious anemia
– Replacement with cyanocobalamin is the goal of therapy.
– A typical schedule is 1 mg IM once a day for 7 days, and then weekly for 1-2
months or until the hemoglobin is normalized. Long-term therapy is 1 mg/mo.
– Symptomatic hypokalemia may occur within 48 hours of initiating therapy,
and supplemental potassium may be needed
• Graves disease
– Antithyroid medications in older patients (>60 y) or in those with underlying
heart disease. When euthyroidism is achieved, radioactive iodine is then
administered.
– Ablation by radioactive iodine administration is the therapy of choice by most
patients (young and healthy).
– The restoration of euthyroidism using antithyroid drugs takes several months.
Patients are evaluated at 6-week intervals by assessing the clinical findings
and serum free T4 and free T3.
• Addison's disease
– Hydrocortisone and fludrocortisone.
– Adjust the hydrocortisone dose depending on patient's
symptoms. Monitor the activity levels of plasma renin to assess
the efficacy of treatment with fludrocortisone and serum
electrolytes.
• Celiac disease
– Place patients on a gluten-free diet.
– Depending on the degree of malabsorption, patients also may
require iron, folate, calcium, or vitamin supplementation.
– In patients whose conditions are severe or refractory, a trial of
prednisone (10-20 mg) may be effective.
• Screening of patients every 1-2 years, until they
are aged 50 years.
– Screening includes an assessment of autoantibodies,
electrolytes, thyroid function tests, liver function
tests, vitamin B-12 levels, Cortrosyn-stimulation test,
fasting blood glucose, plasma renin activity, CBCs,
gonadotropins, and testosterone/estradiol.
• Family members should be strongly considered
for genetic counseling and should undergo
necessary screening for autoimmune diseases.
Polyglandular autoimmune syndrome
type I (PGA-I)
Childhood.
Autosomal recessive pattern, with variable inheritance
No HLA association and,
Equal sex incidence.
Mucocutaneous candidiasis
Hypoparathyroidism
Primary adrenal insufficiency
• Other associated disorders
hypogonadism
hypothyroidism
pernicious anemia
celiac disease
autoimmune hepatitis
alopecia
vitiligo
THANK YOU
