ADDISON'S DISEASE

        ADDISON’S DISEASE

                                                           ( Synonym)ADRENAL INSUFFIENCY

CAUSES:

1.primary- Defect in adrenal gland itself

Secondary-secondary to pituitary defect

Primary

1.infection-TB

2.immunological-auto immune adrenalitis

3.infiltration-amyloid,fungal,malignant,hemochromatosis

4.infarction or hemorrhage-meningococcal

5.Abalation-surgical

6.secondaries in adrenal-metastatic invasion

7.syphilis

8.AIDS

Adrenalin insufficiency occurs when more than90% of the gland is destroyed

Secondary adrenal insufficiency

Hypopituitarism

Hypothalamic disease

Withdrawal of chronic steroid therapy causing suppression of hypothalamic pituitary axis

CLINICAL PICTURES

Due to 1.cortisol deficiency and 2.aldosterone deficiency both put together

3 main features of Adrenal dificiency

1.hypotension

2.hyperpigmentation of skin& mucosa

3.Severe asthenia

Asthenia or severe lassitude is a non specific symptom but is common  and marked.

Hypotension

Mechanism:

Loss of water and potassium(lack of aldosterone) +

Lack of cortisol which has vaso constrictor or pressor effect.

Hypotension-systolic BP is less than100mmof Hg

This is orthostatic hypotension-evident on standing postion not evident while lying down.

Patient c/o giddiness on standing.

Hyperpigmentation

Very characteristic.

It affects skin and buccal mucosa

Skin-over pressure points,creases,scars,knukles, elbow, knee, waist, over the exposed areas.

Already pigmented areas are more pigmented

Pigmentation is due to excess secretion of Melanocyte stimulating hormone by the pituitary

This along with ACTH

Pigmentation is absent in secondary adrenaline insufficiency

Mucosal pigmentation

Prominent over buccal mucosa and anterior aspect of gum.

Timing

In some cases pigmentation may preced other features by many years Hyperpigmentation may not be present in some cases..

Vitiligo may occur in some cases-usually associated with autoimmune adrenalitis.

Severe Asthenia

Other vague complaints are

1.G.I.Tract- nausea,vomiting,diahrrea,anorexia

2.loss of hair in axilla &pubis in females because of loss of adrenergic steroids.

3.Auto immune damage to ovaries/testis-impotence,loss of libido

4.Hypoglycemia related to reduced cortisol which coverts glycogen to glucose.

(cortisol is diabetogenic)

5.Mental symptoms like confusion, irritability, lethargy

6.Intolerence to stress;

In stress patient cannot increase the cortisol output.

So acute exacerbation of symptoms occur with life threatening vascular collapse.

Aldosterone deficiency

1.sodium loss- results from reduced aldosterone  mediated absorbtion of  Na &water consequence-hypovolemia,hypotension,fall in renal flow &uremia

2.Potassium retension- hyper kalemia and ecg chnges and arrhythmias.

Diagnostic features

1.Hypotension

Hyper pigmentation

Differentials for  hyperpigmentation

Pellagra

Malnutrition

Malignancy,irradiation

Drug induced

Thyrotoxicosis

Crohns disease

Ochronosis

Hemochromotosis

Acanthosis nigricans

Arsenic poisoning

Peutz jeghaers syndrome-(intestinal polyposis)

INVESTIGATIONS

Measure levels of Na,K,ACTH and cortisol

4 important investigations

1.low sodium and chloride levels in  blood and hyperkalemia

2.slow excretion of water load

3.low to absent 24 hrs 17 oh  ketosteroids

4. ACTH  stimulation test :poor response to IM injection of corticotrophin

(Tip- all low and slow except hyper kalemia)Water load

If water load is given there is failure to excretit.butdiagnostic value of this test is limited.

ACTH test

ACTH in dose of 25-50 mg is given IV over 8hrs 24 hr urinary excretion of 17-Oh ketosteroids is measured a) the day before the infusion b0 the day after infusion

Similarly serum cortisone level also is measured before and after infusion

Normal response is  3-5 fold rise in urinary corticosteroids

If level remains low throughout –primary

If cortisol is low initially but shows delayed rise-Pituitary cause.

5.Other investigations

ChestXray,(to detect evidence of TB)CT abdomen

Adrenalin antibodies 

TREATMENT

Gluco corticoid replacement is needed inall patients

Cortisol (Hydrocortisone) is given ,not cortisone,because cortisone is to be converted to active  cortisol in the body and its absorption is poor.

Minerelo corticoids need not be replaced in all.

Indication for replacement:

Low sodium,potassium,low BP.

Drug of choice –Fludrocortisone0.05to2mg.

NOTE:

Synthetic glucoteroids like predisolone,prednisone,dexamethasone triamcinalone are not substitute forCortisol because their salt retaining power is poor.

Acute addisonian crisis

Clinically:

Collapse with hypotension

Mental symptoms

Vomiting

Abdominal pain

Cause: untreated patient, stress like infection,trauma,surgerry

or if cortisol level is not raised in acute stress

Treatment of crisis:

IV cortisol

IV saline

Mineralo corticoids.

Mnemonics forAddison’s disease Clinical picture

A-Asthenia

D-dark skin-Hyper pigmentation

D-de pigmentation(vitiligo)Absent in secondary)

I-Intestinal symptoms

S-salt depletion(hyponatremia)

O-orthostatic hypotension

N-neuro psychiatric manifestation

MNEMONIC FOR CAUSES

IAS

I-infection,,infiltration,immunological,invasion,infarction,iotrogenic

A-ablation-surgical

S-syphilis,AIDS

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HYPOTHYROIDISM ,CAUSES CLASSIFICATION,CLINICAL PICTURE,INVESTIGATIONS AND TREATMENT

     

                                             HYPOTHYROIDISM

Hypothyroidism is a syndrome resulting from deficiency of thyroid harmone,causing many metabolic activities to slow down.

 Clinical Classification of hypothyroidism

(Depending on age group of manifestation)

I.                   Cretinism

II.                Juvenile hypothyroidism

III.             Adult hypothyroidism

Cretinism

It is hypothyroidism arising in the new born

Importance-affected children go for irreversible mental and growth retardation,

if not treated in time.

Diagnosis of cretinism

In early stages-recognition is difficult.

Pointers to diagnosis

Protuberant abdomen with umbilical hernia

hoarse cry,sluggish movements,

delayed mile stones mental and growth retardation

low body temperature, obstinate constipation

Treatment

Start replacement therapy within 2 wks of birth

Juvenile hypothyroidism

Hypothroidism manifesting itself around 5-12 yrs

Pathogenesis-

this is thought to be due to presence of ctopic thyroid whose scant production of thyroid harmone is sufficient to meet the needs of infancy and childhood.

But it is insufficient for demands of later childhood.

Diagnosis;

Closely simulates adult myxedema

Distinguishing feature

1.Retarded growth with dwarfism

2.characteristic body proportion

Upper segment exceeds lower segment

(Upper segment is crown to pubic symphysis

Lower segment is pubic symphysis to ground).

Bone age is impaired

Xray shows epiphysial dysgenesis

Stippling instead of single focus

Best seen in head of femur

Confirmation of diagnosis

Elevated TSH ,low T4,T3 Xray evidence of bone retardation.

ADULT HYPOTHYROIDISM AND MYXEDEMA

Hypothyroidism manifesting itself in adults

Usual age incidence is 40yrs;

commoner in females

Terminologies:

Hypothyroidism and myxedema are different nomenclature for the same condition.

In myxedema hydrophilic mucoprotein ground substance isdeposited  in dermis

Classification of hypothyroidism

Classification depending on involvement of pitutory or otherwise.

I.                   Primary

II.                Secondary hypothyroidism

Secondary hypothyroidism -result of pitutory deficiency/hypothalamic problem

Primary  is result  to intrinsic disorder of thyroid gland

Types of primary hypothyroidism

I.                   Spontaneous atrophy

II.                Goitrous

Hashimatosis

Drug induced

Iodine deficiency

Dysharmanogenesis

Iii          Post ablative

iv.         Transient

v.           Sub clinical

Congenital hypothyroidism

·                     Result of thyroid dysgenesis orEctopic thyroid

·                     In born errors of thyroid harmone metabolism

a.       Inability to trap iodine

b.      Inability to organify iodine

c.       Inability to couple iodo thyroxin

Pathology

In Hashimatosis thyroid is shrunken,fibrosed and atrophic

But in goitrogenoues –thyroid is enlarged 

Spontaneous atrophic hypothyroidism

·         It is primary hypothyroidism

·         Organ specific auto immune disorder like Hashimatosis,or graves disease

·         Throid is destroyed,atrophic and fibrosed

·         And associated with lymphoid infiltration

·         At risk of developing other organ specific  autoimmune condtions

·         Associated with diabetes,pernicious anemia,addisons disease.

·         TSH receptor bodies are present which block endogenous TSH

Goitrous Hypothroidism

Associated with goitrous swelling of thyroid gland

Transient type

Found during ist 6 mths after subtotal thyroidectomy

Or radioactive iodine treatment of graves disease

Subclinical hypothyroidism

Asymptomatic patient clinically euthyroid

But on Lab test thyroid harmones are at lower end of normal or TSH  raised

Hashimatos disease

Common cause of goiter

Age-20-60

F>M

Histology: lymphocytic infiltration, fibrosis and follicular cell hyperplasia

Auto immune disorder

Pathophysiology of hypothyroidism

The effects of hypothyroidism are due to 2 things

1.Due to lower metabolic rate

2.Due to increased amount of muco poly saccharide(hyaluronic acid and chondroitin sulphate)

  - ground substance which is deposited in dermis, tongue and vocal cords.

Effect on systems

SKIN

1. Skin –coarse, thickened, dry,cold, pale, and in extreme cases icthyotic

2. Dryness is due to absence of sweating and sebum secretion

3. Wounds on skin heal slowly.

4. Hair on scalp becomes dry, brittle and falls off.

5. Hair loss on outer 2/3 of eye brow

6. Infiltration causes boggy swelling around the eyes

7.  And swelling on dorsum of the hand  ,feet and supraclavicular fossae

8. Skin also gets a yellowish tinge  due to carotene accumulation-reduced metabolism of carotene with reduced rate of conversion of carotene to vitamin

 Symptom of Cold intolerance

CNS

On account of reduces BMR mental retardation (Slow cerebration)

Lethargic symptom

There is also slowed speech

Muscle contraction and relaxation are slowed

Pseudo myotonic reflex occurs(relaxation phase of DTR prolonged)

Carpel tunnel syndrome.

Heart

Bradycardia.

Myocardial contractility is reduced

Heart sounds are muffled

Cardiomegaly-dilatation or pericardial effusion

Gastro intestinal system

constipation

Lipids

High serum levels of triglycerides and cholesterol

The rate of degradation of lipids  is slower than synthesis

So –atherosclerosis accelerated.

Hematology

Anemia

Reproductive system

Menorrhagia –secondary to anovulatory cycles

.In some women with primary hypothyroidism, amenorrhea develops.

Symptoms

tiredness,lethargy,sleepiness,cold intolerance,hoarseness of voice, low pitched deepened  voice,slurred speech,constipation ,loss of apetite

Severity of hypothyroidism

Spectrum of severity occurs

Ranges from severe hypothyroidism with myxedema

to mere suclinical hypothyroidism

Severe cases may progress to Myxedema coma,

precipitating factors-intercurrent infection,cold exposure,trauma norctics

Head to foot examination in moderate to severe myxedema.

Dull expressionless face with-

Periorbital puffiness

Sparse hair,alopecia

Dry hair

Loss of hair in lateral 1/3rd of eyebrow

Coarse features

Thick lip

Large tongue

Pale  cool rough  skin

Non pitting edema of skin of hands,feet and eye lids.

Deep hoarse voice

deafness

Complication

Myxedema (severe hypothyroidism)

Progress to hypothermic stuperous state called Myxedema coma

Investigations

Serum T3 concentration decreased

Serum T4 concentration decreased

Serum  TSH level raised

Serum TSH level low in pitutory or hypothalamic variety

(Normal level of Thyroid hormones 

Note:From lab to lab reference  range vary

T4- 4-12 µ.gms/100 ml

T3- 80 -200 nano gm/100ml

TSH- 0.5 -5µU/litre)

Treatment

Levo thyroxin sodium 100 µgm per day

Initial daily dose25 µgm /day

At 2-3 wks interval increase by 25-50 µgm.-

Until TSH is within normal range

Usual range is 100-150 µgm /day

 In Secondary hypothyroidism:

First treat adrenal insuffiency ,only then thyroxine must be started

Myxedema coma-Emergency treatment

Rapidly give levothyroxin intravenously over 5 min-

 Add dexamethazone2mg IVorPO every 6 hrs

Then give levothyroxine 100 µgm/day PO or IV  until patient is stabilized.

Simultaneously treat hypovolemia and electrolyte abnormalities

Mechanical ventilation as needed.

Treat hypothermia;/infections

Avoid sedative,narcotics, anesthesia

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HYPER THYROIDISM- causes ,Clinical features,investigations and treatment

                HYPERTHYROIDISM

Hyper thyroidism is a condition resulting from excessive production of thyroid hormone by the thyroid gland.

Thyrotoxicosis is acondtion due to excessive production of thyroid hormone from any cause .

Thyrotoxicosis and hyperthyroidism  are terms often used interchangeably

systemic examination in Hyperthyroidism

Nervous system:

Nervousness,feeling of internal tension
Depression
tremors
brisk reflexes
emotional instability
 inability to get along with others

poor at school and work

Cardio vascular system
High blood pressure
Tacchy cardia,/
supraventricular tachycardia-on account of direct action upon the conduction system
atrial fibrillation can be superimposed on underlying heart disease
long standing hyperthyroidism can  cause cardiomegaly and cardiac failure
this is due to hyperdynamic state
flow murmur-systolic
Pleuro pericardial rub in Graves disease
Means-lermans scratch-mid systolic scratching sound-at upper part of sternum-at end expiration(rare)
dyspnea on effort
angina on effort

EYES:Ophthalmopathy:

 can  precede,accompany or follow  Graves disease 
 i.e.ophthalmopathy runs  a course independent of Graves Disease.cause is auto immune mechanism
Sympathetic overtone causes retraction of upper eyelid and so wide palpebral  fissure

Von Grafes sign:
 infiltration of inflammatory cells occurs over external ocular muscles producing swelling of the muscles and fibrosis causing restriction of ocular motility and diplopia

Mobius sign:in ability to converge the eyes

Lid lag-Stellwags  sign-ask the patient to look up and then downwards-eye ball rotates down first upper lid lags behind.

Exophthalmoses/proptosis:Protrusion of eye ball from the orbit,exposing sclera  below  and above cornea Made out by asking the patient to look straight ahead and watching  from the side. Retrobulbar deposition of  immune complexes and inflammatory cells produces exophthalmos
Exposed cornea can go for keratitis 
Pressure on optic nerve or keratitis can cause blindness. Proptosis also causes  edema or chemosis of conjunctiva.
Rarely ophthalmopathy can can occur in Euthyroid patient(called Euthyroid Graves disease) or Hashimatos ophthalmopathy is one of the 3 components  of Graves disease.

 components of Graves Disease :
hyperthyroidism
Ophthalmopathy
Pretibial myxedema

ophthalmopathy may not correlate with severity of  hyperthyroidism.

Gastro Intestinal system

Increased appetite but weight loss

Hyper defecation because of rapid motility 

diarrhea uncommon

In advance hyperthyroidism malnutrition can cause abnormal Liver function 

Reproductive System

In female infertility/oligomenorrheaIn 

males-reduced sperm count and impotence and Gynecomatia because of increased peripheral conversion of androgen to estrogen  inspite of  hige testosterone level

Thryoid hormone increase sex hormone binding globulinSo inceased level of total testosterone and estrogen level

But serum LH(leutinising hormone) and FSH may be normal or increased

Musculo skeletal system

Excessive muscle catabolism causes atrophy and weakness of muscles

sssProximal muscle weakness,Hypokalemic periodic paralysis may occur

Myesthenia gravis

bone resorption is more than bone formation causing-hyper calcemia and hyper calciuria

Longstanding cases-osteopenia

Metabolic system

weight loss common especially in elderly with anorexia

Teenagers and young adults can loose control over appetite and gain weight 

Increased heat production is dissipated by increased sweating and mild polydipsia 

aversion for heat and preference for cold temperature

Insulin requirement in DM increases.

Skin

 Skin is warm ,moist,velvety

palms are warm and sweating

Onycholysis of the nails -(retraction of nails from nail bed) occursa nd indicates long standing disease. 

Pretibial myxedema

Peu d' orange appearance of the skin over pretibial area(appearance of dimpled texture of an orange peel.

Other areas involved are -dorsum of the foot,great toe/deltoid region

lesions are erythematous or violacoius in colour

May follow hyperthyroidism after treatment

It is due to mucoid swelling of the dermis and subcutaneous tissue.

Thyroid gland

usually enlarged

can be diffuse enlargement or multi nodular or uninodular

Causes of hyperthyroidism

1.Auto antibody induced -Graves disease

2.Toxic nodular goitre

3.Neo natalAutonomous  tumor

4.Toxic adenoma

5.well differentiated thyroid carcinoma

6.Leakage of iodoprotein from damaged follicles

7.diffuse lymphocytic thyroiditis

8.Dequervains disease-subacute thyroiditis

9.Thyroiditis-Transient hyperthyroidism can occur in -

10.thyroiditis (by viral or bacterial infection or rarely in TB

11.Excessive TSH  secretion-

tumor of pitutory thyrotrophs,Hydatiform mole,Chorio carcinoma,Embriyonal carcinoma of testes

12.ADMINISTRATION OF THYROID HORMONE Intensional(factitious)

13.Over enthusiastic therapy

14. Iodide induced -certain  iodine containing medicines if used long periods can cause hyperthyroidism

15.Jod basedow syndromeIodide induced -

certain  iodine containing medicines if used long periods can cause hyperthyroidism

Radiographic contrast media

HEAD TO FOOT EXAMINATION IN HYPERTHYROIDISM
 scalp-Alopacia
 Eyes- Exophthalmos
lidlag,-Stellwags sign
lid retraction,-Von graffes sign
failure of convergence mobius sign
Neck:
thyroid enlargement with bruit
(diffuse,uninodular or multinodular)

Chest:

gynecomatia

spidernevi

cardiomegaly 

early sytolis murmur in  pulmonary area

Means-lermans scratch-mid systolic scratching sound-at upper part of sternum-at end expiration(rare)

Pleuro pericardial rub

Abdomen

hyperphagia,

hyper defecation

splenomegaly

 Genito urinary system

Impotence,infertility, oligo menrrhea

Lower limbs
proximal muscle weakness
periodic hypokalemic paralysis
Mysthenia gravis
Legs
Pretibial myxedema
(peu 'd orange raised plaque)
Fingers 
 fine tremors
clubbing-periosteal bone thickening of  distal phalanx
onycholysis
Palmar erythema
Digital pulsation
Pulse
tachycardia
increase in sleeping pulse rate
atrial fibillation
BP
High systolic BP
Skin:
smooth velvety ,moist sweating, warm
onycholysis-retraction of nail from nail bed

THYROID STROM:

An uncommon complication of  hyperthyroidism

Precipitated by conditions like infection,anesthesia

Suddenly symptoms worsen  causing

high temperature, confusion and can result in death.

INVESTIGATIONS

assess levels of

·         TSH-In hyperthyroidism TSH levels fall

·         T3

·         T4

sometimes T4 may be normal T3 can be high

False high levels may occur in pregnancy or due to oral contraceptives

Low T4 levels occur  in-corticosteroid therapy,severe illness-in these,T4 binding proteins level go down.

·         Thyroid antibodies-to diagnose auto immune cause/graves disease

Normal level of Thyroid hormones 
Note:From lab to lab reference  range vary
T4- 4-12 µ.gms/100 ml
T3- 80 -200 nano gm/100ml
TSH- 0.5 -5µU/litre

·         IMAGING TESTS

1.Ultra sound of thyroid to  look for thyroid nodules

2.Thyroid scan using radioactive iodine-to ascertain size,shape and position of thyroid gland.

3.Radioactive iodine uptake test-to check thyroid function and cause of hyperthyroidism

4.Fine needle aspiration biopsy of nodule to check or rule out  malignancy.

Treatment of hyperthyroidism

Options

1.Medical treatment

2.Radioactive Iodine

3.Thyroid surgery

No single treatment works for every one.

 Factors influencing treatment:

1.age

2.possible allergies

3.Side effects of medicines

4.conditions like pregnancy,heart disease

Medical therapy

1.Beta blockers:

Usefull for symptomatic treatment: tremors,tachycardia,nervousness until other treatments take effect

2.Antithyroid medicines

Methimazole

Methimazole can harm the fetus

In pregnancy first 3 months- useful drug is propyl thiouracil

Antithyroid medicines do not provide permanent cure:take weeks or months to take effect-

They are not useful in thyroditis

 Side effects of antithyroid medicines

Allergy,-skin rash,itching

neutropenia manifest with sorethraot,fever

liver failure(rare)-causes jaundice

Methimazole is contra indicated in agranulocytosis,allergy and liver diseases.

3.Radiactive iodine therapy

Common and effective mode of treatment

Radioactive iodine 131 orally as capsule or liquid-

Destroys the hyperactive  cells of thyroid gland

But do not affect other body tissues

Undesirable later  sequlae –hypothyroidism

Contraindicated in pregnancy and during breast feeding

Thyroid surgery

Least used mode of therapy

Removal of part of or most of thyroid .

Indications :

1.Large goiters

2.pregnancy

Pregnant women where radioactive  and antithyroid medicines are contra indicated

Preparatory to surgery antithyroid medicines are given to bring thyroid level to normalcy-this to prevent 

possible thyroid strom which can be precipitated by general anesthesia.

Post surgically hypothyroidism may develop-to be treated with thyroid hormone.

Diet prescription in hyper thyroidism

Avoid  food containing large amount of iodine likeseaweed

Avoid iodine suppliments

Avoid also cough syrups and multi vitamins containing iodine.

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