HYPERTHYROIDISMHYPERTHYROIDISM(THYROTOXICOSIS)(THYROTOXICOSIS)

THYROTOXICOSIS THYROTOXICOSIS & & HYPERTHYROIDIDMHYPERTHYROIDIDM

ThyrotoxicosisThyrotoxicosis = = the clinical sdr that results when the clinical sdr that results when tissues are exposed to high levels of circulating tissues are exposed to high levels of circulating TH TH

HyperthyroidismHyperthyroidism = = the manifestations result from the manifestations result from overproduction of hormoneoverproduction of hormone by the thyroid gland by the thyroid gland itself itself

Classification of Classification of ThyrotoxicosisThyrotoxicosis

Thyrotoxicosis with HyperthyroidismThyrotoxicosis with Hyperthyroidism Grave’s diseaseGrave’s disease Toxic multinodular goiterToxic multinodular goiter Toxic adenomaToxic adenoma Iodine-induced (Jod-Basedow)Iodine-induced (Jod-Basedow) TSH-secreting pituitary adenomaTSH-secreting pituitary adenoma

Thyrotoxicosis without HyperthyroidismThyrotoxicosis without Hyperthyroidism

Thyrotoxicosis factitia (Thyrotoxicosis factitia (← iatrogenic or voluntary ingestion of ↑ T4 or TH ← iatrogenic or voluntary ingestion of ↑ T4 or TH preparation ) preparation )

Subacute thyroiditisSubacute thyroiditis Thyroiditis with transient thyrotoxicosis Thyroiditis with transient thyrotoxicosis (silent, postpartum thyroiditis, Hashytoxocosis) (silent, postpartum thyroiditis, Hashytoxocosis) Ectopic thyroid tissue (struma ovari )Ectopic thyroid tissue (struma ovari )

Forms of hyperthyroidism Forms of hyperthyroidism

11. . BASEDOW-GRAVES’ DISEASE BASEDOW-GRAVES’ DISEASE the most common form of thyrotoxocosisthe most common form of thyrotoxocosis =diffuse goiter, thyrotoxicosis, infiltartive ophtalmophathy +/_ infiltrative =diffuse goiter, thyrotoxicosis, infiltartive ophtalmophathy +/_ infiltrative

dermopathy (5-10%)dermopathy (5-10%) Is an autoimmune disease of unknown causeIs an autoimmune disease of unknown cause Pathogenesis Pathogenesis : the major atg of Grave’s disease is TSH-R: the major atg of Grave’s disease is TSH-R T- Ly become sensitized to atgs within the thyroid gland and (+) B-Ly to T- Ly become sensitized to atgs within the thyroid gland and (+) B-Ly to

synthesize antibodies (Abs ) to these antigens; TSHRAbs (Abs directed synthesize antibodies (Abs ) to these antigens; TSHRAbs (Abs directed against the TSH rec- the thyroid cell membrane = TSI )against the TSH rec- the thyroid cell membrane = TSI )→ thyroid growth, ↑ → thyroid growth, ↑ vascularity, ↑ rate of thyroid hormone production and secretionvascularity, ↑ rate of thyroid hormone production and secretion

! There is an underlying genetic predisposition, but it is not clear what “ ! There is an underlying genetic predisposition, but it is not clear what “ triggers “the acute episode triggers “the acute episode

Some factors that may incite the acute episode : psychological stress, Some factors that may incite the acute episode : psychological stress, pregnancy, particularly the postpartum period pregnancy, particularly the postpartum period

FORMS OF THYROTOXICOSISFORMS OF THYROTOXICOSIS

2. 2. TOXIC ADENOMA (Plummer’s disease)TOXIC ADENOMA (Plummer’s disease)

= a functioning adenoma= a functioning adenoma hypersecreting T3, T4; these lesions hypersecreting T3, T4; these lesions start out as a small autonomously functionig nodule that slowly start out as a small autonomously functionig nodule that slowly increases in size to produce excessive quantities of THincreases in size to produce excessive quantities of TH→gradually →gradually suppresses endogenous TSH secretion → reduced function of the suppresses endogenous TSH secretion → reduced function of the contralateral lobe of the glandcontralateral lobe of the gland

PathogenesisPathogenesis: several mutations in the TSH-rec gene → : several mutations in the TSH-rec gene → constitutive activation of the TSH rec in the absence of TSHconstitutive activation of the TSH rec in the absence of TSH The tipical patient is an older individual (usually> 40)The tipical patient is an older individual (usually> 40) tyrotoxicosis + palpable /not palpable thyroid lumptyrotoxicosis + palpable /not palpable thyroid lump The cardiovascular manifestations may be prominent; infiltrative The cardiovascular manifestations may be prominent; infiltrative

ophatalmopathy or dermopathy are never present!!!ophatalmopathy or dermopathy are never present!!! Physical examination reveals a definite nodule on one side, with Physical examination reveals a definite nodule on one side, with

very little thyroid tissue on the other side very little thyroid tissue on the other side

FORMS OF THYROTOXICOSISFORMS OF THYROTOXICOSIS 3. TOXIC MULTINODULAR GOITER3. TOXIC MULTINODULAR GOITER

Usually occurs in older patients with long standing euthyroid multinodular goiter,Usually occurs in older patients with long standing euthyroid multinodular goiter,from which it emerges slowly ; the increase in the extent of autonomous functionfrom which it emerges slowly ; the increase in the extent of autonomous functioncause the disease to move from the nontoxic to the toxic phasecause the disease to move from the nontoxic to the toxic phase Physical examination : reveals a multinodular goiter + manifestations of Physical examination : reveals a multinodular goiter + manifestations of hyperthyroidism, without signs of autoimmunity hyperthyroidism, without signs of autoimmunity

→ → older individuals older individuals

4. IODINE-INDUCED HYPERTHYROIDISM4. IODINE-INDUCED HYPERTHYROIDISM → → adm. of supplemental iodine to subjects with endemic iodine deficiency goiter → in adm. of supplemental iodine to subjects with endemic iodine deficiency goiter → in

iodine-induced hyperthyroidism and even Grave’s disease iodine-induced hyperthyroidism and even Grave’s disease Causes :Causes :amiodarone ( contains 37% iodine), coronarography , IVU, CT amiodarone ( contains 37% iodine), coronarography , IVU, CT

( radiographyc contrast media)( radiographyc contrast media) Thyrotoxicosis + diffuse or multinodular goiterThyrotoxicosis + diffuse or multinodular goiter Confirmation that the patient has been exposed to large quantities of iodine :Confirmation that the patient has been exposed to large quantities of iodine : ↓ ↓ RAIURAIU ↑ ↑urinary iodine excretion (>several mg/day)urinary iodine excretion (>several mg/day)

5. TSH-SECRETING PITUITARY ADENOMA5. TSH-SECRETING PITUITARY ADENOMA rarerare goiter + hyperthyroidism goiter + hyperthyroidism

FORMS OF THYROTOXICOSISFORMS OF THYROTOXICOSIS 6. SUBACUTE AND SILENT, POSTPARTUM 6. SUBACUTE AND SILENT, POSTPARTUM

THYROIDITIS THYROIDITIS

mildmild→ severe thyrotoxicosis, following an acute release of → severe thyrotoxicosis, following an acute release of T4, T3 into circulation T4, T3 into circulation

!!! These illness can be differentiated from others forms of !!! These illness can be differentiated from others forms of thyrotoxicosis in that RAIU is ↓↓ and the symptoms usually thyrotoxicosis in that RAIU is ↓↓ and the symptoms usually subside spontaneously over a period of weeks or monthsubside spontaneously over a period of weeks or month

7.7. STRUMA OVARYSTRUMA OVARY A teratoma of the ovary contains thyroid tissue that becomes A teratoma of the ovary contains thyroid tissue that becomes

hyperactivehyperactive! No goiter or eye signs! No goiter or eye signsRAIU over the neck is RAIU over the neck is ↓; total body scan reveals uptake of I131 in the ↓; total body scan reveals uptake of I131 in the

pelvispelvis

Clinical featuresClinical features Effects on – cardiovascular system, CNS, gastrointestinal tube , neuromuscular system, lipid, Effects on – cardiovascular system, CNS, gastrointestinal tube , neuromuscular system, lipid,

protein, carbohydrate metabolismsprotein, carbohydrate metabolisms

1.GENERAL MANIFESTATIONS 1.GENERAL MANIFESTATIONS The stimulation of energy metabolism and heat production is reflected in the The stimulation of energy metabolism and heat production is reflected in the ↑ basal metabolic rate. ↑ basal metabolic rate.

↑ appetite and heat intolerance and in a sometimes slightly elevated basal body temperature (↑ appetite and heat intolerance and in a sometimes slightly elevated basal body temperature ( 37- 37-37.5°C), sweating37.5°C), sweating

2. Nervous system 2. Nervous system Alterations in NS function are manifested by:Alterations in NS function are manifested by:

Emotional lability, nervousness, irritability Emotional lability, nervousness, irritability Insomnia, restlessness, shortness of attention spanInsomnia, restlessness, shortness of attention span Fine, rhytmic tremor of the hands, tongue, or slightlly closed eyelids Fine, rhytmic tremor of the hands, tongue, or slightlly closed eyelids Hyperkinesia Hyperkinesia hyperreflexia ( hyperreflexia ( an increase in the speed of muscle contraction and relaxation) an increase in the speed of muscle contraction and relaxation) 3. CARDIOVASCULAR SYSTEM3. CARDIOVASCULAR SYSTEM ! TH have marked positive inotropic and chronotropic effects on the heart ! TH have marked positive inotropic and chronotropic effects on the heart → accounts for the increased → accounts for the increased

cardiac output and ↑↑ in heart rate in hyperthyroidism; TH increase the number of beta-adrenergic receptors cardiac output and ↑↑ in heart rate in hyperthyroidism; TH increase the number of beta-adrenergic receptors in heart muscle ( and also skeletal muscle, adiposse tissue) in heart muscle ( and also skeletal muscle, adiposse tissue) the most common complaints: the most common complaints:

palpitationspalpitations tachycardia is almost always present.tachycardia is almost always present. heart sounds are loud and ringing; functional systolic murmurs may also be heard in different areas heart sounds are loud and ringing; functional systolic murmurs may also be heard in different areas

of ausculatation (mostly at the apex) (usually abate when a normal metabolic state is restored) of ausculatation (mostly at the apex) (usually abate when a normal metabolic state is restored) cardiac arrhythmias are almost invariably supraventricular (extrasistolia, atrial fibrillation, cardiac arrhythmias are almost invariably supraventricular (extrasistolia, atrial fibrillation,

paroxysmal supraventricular tahycardia, )paroxysmal supraventricular tahycardia, ) widening of pulse pressure ( widening of pulse pressure ( ↑ systolic TA ← ↑cardiac output; ↓ diastolic pressure ↑ systolic TA ← ↑cardiac output; ↓ diastolic pressure ↓ peripheral ↓ peripheral

vascular resistance )vascular resistance ) hyperkinetic cardiovascular syndrome hyperkinetic cardiovascular syndrome ↑ cardiac output , ↑ heart rate ( ↑ TA) and ↓peripheral ↑ cardiac output , ↑ heart rate ( ↑ TA) and ↓peripheral

vascular resistance → ↓diastolic pressurevascular resistance → ↓diastolic pressure

Clinical featuresClinical features 44. DIGESTIVE MANIFESTATIONS . DIGESTIVE MANIFESTATIONS

An increase in appetite but with weight loss( An increase in appetite but with weight loss( ←← because of the because of the increased basal metbolic rate)increased basal metbolic rate)

TH (+) gut motility TH (+) gut motility increased motility ( stools are frequently soft , but increased motility ( stools are frequently soft , but diarrhea is rare)diarrhea is rare)

Hepathic dysfunction occurs, particularly when thyrotoxicosis is Hepathic dysfunction occurs, particularly when thyrotoxicosis is severesevere

5. MUSCULAR EFFECTS 5. MUSCULAR EFFECTS ! Although TH (+) increased synthesis of many structural proteins, in ! Although TH (+) increased synthesis of many structural proteins, in

hyperthyroidism there is increased protein turnover and loss of hyperthyroidism there is increased protein turnover and loss of muscle tissue or myopathymuscle tissue or myopathy Weakness and fatigability ; weakness is most prominent in the Weakness and fatigability ; weakness is most prominent in the

proximal muscles of limbs, causing difficulty in climbing stairs ( “ chair proximal muscles of limbs, causing difficulty in climbing stairs ( “ chair sign”) sign”)

In severe untreated cases, muscle wasting (proximal) develops out of In severe untreated cases, muscle wasting (proximal) develops out of proportion = thyrotoxic myopathyproportion = thyrotoxic myopathy

6. ENDOCRINE manifestation6. ENDOCRINE manifestation Menstrual abnormalities: ovulation may be impaired, oligomenorrhea, Menstrual abnormalities: ovulation may be impaired, oligomenorrhea,

secondary amenorrheasecondary amenorrhea In M: erectile dysfunction, gynecomastia In M: erectile dysfunction, gynecomastia

Clinical manifestationsClinical manifestations 7. EYES7. EYES- Retraction of the upper eyelidRetraction of the upper eyelid that lead to widening of the palpebral that lead to widening of the palpebral

fissure so that the sclera are exposed above the superior margin of fissure so that the sclera are exposed above the superior margin of limbus ( limbus ( adrenergic stimulation of the upper eyelid)= common in all adrenergic stimulation of the upper eyelid)= common in all forms of thyrotoxicosis, regardless of the underlying cause and is forms of thyrotoxicosis, regardless of the underlying cause and is responsible for responsible for the bright-eyed “ starethe bright-eyed “ stare” of the patient with ” of the patient with thyrotoxicosis thyrotoxicosis

- Lid lagLid lag= the upper lid lags behind the globe when the patient is asked to = the upper lid lags behind the globe when the patient is asked to gaze slowly downwardgaze slowly downward

- Globe lagGlobe lag= when the globe lags behind the upperlid when the patient = when the globe lags behind the upperlid when the patient gazes slowly upward gazes slowly upward

- A fine tremor of the lightly closed lidsA fine tremor of the lightly closed lids can often be observed= can often be observed= Rosenbach’ s signRosenbach’ s sign

= Class 1 (O) of the Werner’s classification of eye signs in Graves’ = Class 1 (O) of the Werner’s classification of eye signs in Graves’ disease disease

! ! These ocular manifestations appear to be the result of ↑ adrenergic These ocular manifestations appear to be the result of ↑ adrenergic activityactivity. It is important to differentiate these ocular manifestations, . It is important to differentiate these ocular manifestations, which occur in all forms of thyrotoxicosis, from those of infiltrative which occur in all forms of thyrotoxicosis, from those of infiltrative orbitopathy, which are characteristic of hyperthyroid Graves’ disease. orbitopathy, which are characteristic of hyperthyroid Graves’ disease. These manifestations will often abate when the thyrotoxicosis is These manifestations will often abate when the thyrotoxicosis is relieved. relieved.

Clinical featuresClinical features 8.SKIN and HAIR 8.SKIN and HAIR - warm, moist, pink skin (- warm, moist, pink skin (← cutaneous vasodilatation and excessive sweating); the ← cutaneous vasodilatation and excessive sweating); the

patient blushes readilypatient blushes readily- The hair is fine and friable and hair loss may be excessive; the nails are often The hair is fine and friable and hair loss may be excessive; the nails are often

soft and friable soft and friable

ASSOCIATED DISEASES ASSOCIATED DISEASES DM Type 1DM Type 1 CSR ICSR I vitilligo, celiac disease, myastenia gravisvitilligo, celiac disease, myastenia gravis

GoiterGoiter Graves’ disease– the goiter is diffuse and usual symmetrical; the consistency Graves’ disease– the goiter is diffuse and usual symmetrical; the consistency

varies from soft to firm and rubbery; the surface is generally smooth; in severe varies from soft to firm and rubbery; the surface is generally smooth; in severe cases, a thrill may be felt, usually over the upper poles, and a thrill is always cases, a thrill may be felt, usually over the upper poles, and a thrill is always accompanied by an audible bruit ( the thrills and bruits accompanied by an audible bruit ( the thrills and bruits ↑ blood flow and are ↑ blood flow and are usually continuous but sometimes are present only in systole)usually continuous but sometimes are present only in systole)

Toxic adenoma ; a firm nodule on one side with little thyroid tissue on the other Toxic adenoma ; a firm nodule on one side with little thyroid tissue on the other side side

Toxic multinodular goiter – multinodular goiter that may be small or quite large Toxic multinodular goiter – multinodular goiter that may be small or quite large and may even extendly substernally; consistency: firm the surface: and may even extendly substernally; consistency: firm the surface: inhomogeneousinhomogeneous

Clinical featuresClinical features

INFILTRATIVE ORBITOPATHY of GRAVES’DISEASEINFILTRATIVE ORBITOPATHY of GRAVES’DISEASE

precedes, follows or its onset is simultaneous with precedes, follows or its onset is simultaneous with thyrotoxic manifestationsthyrotoxic manifestations

More frequently in womenMore frequently in women More severe in menMore severe in men bi/unilateral, symmetrical / asymmetrical bi/unilateral, symmetrical / asymmetrical Clinic Clinic : irritation in the eyes, excessive tearing that is often : irritation in the eyes, excessive tearing that is often

made worse by exposure to air or wind, exophtalmos, made worse by exposure to air or wind, exophtalmos, periorbital edema, double vision, photophobia…periorbital edema, double vision, photophobia…

PathogenesisPathogenesis: the extraocular muscle and adipose tissue are : the extraocular muscle and adipose tissue are swollen by the accumulation in the extracellular matrix of swollen by the accumulation in the extracellular matrix of GAG that are secreted by fibroblasts under the influence of GAG that are secreted by fibroblasts under the influence of citokines from local citokines from local Ly, sensitized to a common antigen Ly, sensitized to a common antigen such as the TSH-Recsuch as the TSH-Rec ( that is found in orbital fibroblasts, ( that is found in orbital fibroblasts, orbital muscle and thyroid tissue) . This accumulation orbital muscle and thyroid tissue) . This accumulation disrupts and impairs the function of muscle disrupts and impairs the function of muscle diplopia and diplopia and leads to proptosis; proinflammatory citokines also leads to proptosis; proinflammatory citokines also redness, congestion and conjunctival and periorbital redness, congestion and conjunctival and periorbital edema. As the disease runs its course and inflammation edema. As the disease runs its course and inflammation ↓, ↓, the damaged muscle become fibrosed. the damaged muscle become fibrosed.

Clinical featuresClinical features WERNER’S CLASSIFICATION OF EYE CHANGES IN GRAVE’S DISEASEWERNER’S CLASSIFICATION OF EYE CHANGES IN GRAVE’S DISEASE

class 0 (N) : no signs or symptomsclass 0 (N) : no signs or symptoms

class 1 (O) – only signs, no symptoms ( signs limited to upper lid retraction, stare, lid lag, class 1 (O) – only signs, no symptoms ( signs limited to upper lid retraction, stare, lid lag, globe lag…)globe lag…)

class 2 (S) :soft tissue involvement:periorbital edema, irritation in the eyes, excesive class 2 (S) :soft tissue involvement:periorbital edema, irritation in the eyes, excesive tearing, conjunctival congestion or edema (chemosis), enlarged lacrimal glands ; proptosis tearing, conjunctival congestion or edema (chemosis), enlarged lacrimal glands ; proptosis <22mm <22mm

Class 3 (P): proptosis >=22mmClass 3 (P): proptosis >=22mm

Class 4 (E)– extraocular muscle involvement Class 4 (E)– extraocular muscle involvement diplopia; ophtalmoplegia (especially of diplopia; ophtalmoplegia (especially of upward gazeupward gaze← affection of the inferior rectus); weakness of the extraocular muscles is ← affection of the inferior rectus); weakness of the extraocular muscles is evident in the patient’s inability to achieve or maintain convergence.evident in the patient’s inability to achieve or maintain convergence.

Class 5 (C) – corneal involvement (keratitis) due to inability to close the eyes completely Class 5 (C) – corneal involvement (keratitis) due to inability to close the eyes completely =lagophthalmos ( proptosis >32mm),=lagophthalmos ( proptosis >32mm),

Class 6 (S) – sight loss (optic nerve involvement) Class 6 (S) – sight loss (optic nerve involvement) ← likely due to ischemia of the nerve ← likely due to ischemia of the nerve from compression of the surrounding enlarged extraocular musclesfrom compression of the surrounding enlarged extraocular muscles

Clinical featuresClinical features !Classes 2-6 represents true infiltrative disease !Classes 2-6 represents true infiltrative disease

involving orbital muscle and orbital tissues and involving orbital muscle and orbital tissues and are specific to Graves’ disease..

INFILTRATIVE DERMOPATHY (PRETIBIL INFILTRATIVE DERMOPATHY (PRETIBIL MYXEDEMA)MYXEDEMA)

RareRareHyperpigmented, nonpitting induration of the skin of the legs, Hyperpigmented, nonpitting induration of the skin of the legs,

commonly over the pretibial areacommonly over the pretibial area

Laboratory findingsLaboratory findings

11. . HORMONAL ASSESSEMENTHORMONAL ASSESSEMENT TSHTSH//↓↓↓↓, T3, T3, T4, T4 (FT4) (FT4 =the unbound portion, is the active part) (FT4) (FT4 =the unbound portion, is the active part) exception: TSH-secreting pituitary adenoma: exception: TSH-secreting pituitary adenoma: ↑ TSH, FT4↑↑ TSH, FT4↑

2. IMAGISTIC INVESTIGATIONS2. IMAGISTIC INVESTIGATIONS Thyroid ultrasonographyThyroid ultrasonography

Graves’ disease – diffuse thyroid hypertrophya, homogenous aspect; Graves’ disease – diffuse thyroid hypertrophya, homogenous aspect; hipoechoichipoechoic

Toxic adenoma/toxic multinodular goiter– one nodule/ enlarged gland that is Toxic adenoma/toxic multinodular goiter– one nodule/ enlarged gland that is diffusely inhomogeneous with multiple individual nodulesdiffusely inhomogeneous with multiple individual nodules

RAIU RAIU 131131I – I – ↑ values ↑ values in thyrotoxicosis with hipertiroidism (2h-10-15%, 24h-45-50%)in thyrotoxicosis with hipertiroidism (2h-10-15%, 24h-45-50%) ↓ ↓ values in subacute thyroiditis or “ silent thyroiditis”, iodine-induced values in subacute thyroiditis or “ silent thyroiditis”, iodine-induced

hyperthyroidismhyperthyroidism

THYROID SCINTHYGRAPHY ( RADIOIODINE SCANTHYROID SCINTHYGRAPHY ( RADIOIODINE SCAN)) Graves’disease – enlarged gland that is usually rather symmetric with a Graves’disease – enlarged gland that is usually rather symmetric with a

typically very homogenous distribution of tracertypically very homogenous distribution of tracer Toxic adenoma – a “ hot “ nodule with Toxic adenoma – a “ hot “ nodule with ↓ or absent function of the contralateral ↓ or absent function of the contralateral

lobelobe Toxic multinodular goiter – multiple functioning nodules in the gland or Toxic multinodular goiter – multiple functioning nodules in the gland or

occasionally an irregular, patchy distribution of radioactive iodineoccasionally an irregular, patchy distribution of radioactive iodine

Laboratory findingsLaboratory findings 3. OTHERS3. OTHERS glycemia normal, IGT, DMglycemia normal, IGT, DM cholesterolcholesterol n/ n/ AF AF ECG – sinus tachycardia, AF, SVT, LVHECG – sinus tachycardia, AF, SVT, LVH TRAbs(+) TRAbs(+) –are –are relatively specific to Graves’ diseaserelatively specific to Graves’ disease; useful in ; useful in

patients who presents with unilateral or bilateral exophtalmos patients who presents with unilateral or bilateral exophtalmos without obvious signs or laboratory manifestations of Graves’ without obvious signs or laboratory manifestations of Graves’ disease; useful indicator of the degree of disease activity and the disease; useful indicator of the degree of disease activity and the level of TRAbs correlates with the severity of the eye diseaselevel of TRAbs correlates with the severity of the eye disease

TPO Abs and TG Abs TPO Abs and TG Abs are usually present in both Graves’ are usually present in both Graves’ disease and Hashimoto thyroiditisdisease and Hashimoto thyroiditis

ULTRASONOGRAPHY, CT and MRI scan of the orbita ULTRASONOGRAPHY, CT and MRI scan of the orbita : reveal : reveal extraocular muscle enlargement in most patients with Graveas’ extraocular muscle enlargement in most patients with Graveas’ diseasedisease

ComplicationsComplications THYROTOXIC CRISIS (“ THYROID STORM”)THYROTOXIC CRISIS (“ THYROID STORM”)

= the acute exacerbation of all of the symptoms and signs of thyrotoxicosis; life-= the acute exacerbation of all of the symptoms and signs of thyrotoxicosis; life-threatening threatening

Fever (38-41Fever (38-41ºC), ºC), cardiac arrhythmias , heart failure, diarrhea, vomiting, marked cardiac arrhythmias , heart failure, diarrhea, vomiting, marked agitation, delirium, comaagitation, delirium, coma

THYROTOXIC CARDIAC INVOLVEMENT (CARDIOTHYREOSIS) THYROTOXIC CARDIAC INVOLVEMENT (CARDIOTHYREOSIS) cardiac arrhythymias– AFcardiac arrhythymias– AF Heart failureHeart failure Myocardial ischaemia Myocardial ischaemia

THYROTOXIC MYOPATHYTHYROTOXIC MYOPATHY

THYROTOXIC OSTEOPOROSIS THYROTOXIC OSTEOPOROSIS

DIABETES MELLITUSDIABETES MELLITUS

THYROTOXIC HEPATHOPATHY THYROTOXIC HEPATHOPATHY Hepatic dysfunction occurs particularly when thyrotoxicosis is severe – jaundice, Hepatic dysfunction occurs particularly when thyrotoxicosis is severe – jaundice,

hepaomegaly, hepaomegaly, ↑ ALT↑ ALT

TREATMENT OF HYPERTHYROIDISMTREATMENT OF HYPERTHYROIDISM

! Although autoimmune mechanisms are responsible for the syndrome ! Although autoimmune mechanisms are responsible for the syndrome of Graves’ disease, managements has been largely directed toward of Graves’ disease, managements has been largely directed toward controlling the hyperthyroidismcontrolling the hyperthyroidism

Methods of treatment;Methods of treatment; 1. Medical treatment- Antithyroid drug therapy1. Medical treatment- Antithyroid drug therapy 2. Surgery2. Surgery 3. Radioactive iodine therapy3. Radioactive iodine therapy

TREATMENT OF HYPERTHYROIDISMTREATMENT OF HYPERTHYROIDISM Medical treatmentMedical treatment

Anthithyroid drugs (ATS) Anthithyroid drugs (ATS) Mechanisms of actionMechanisms of action: : ( - ) TPO-mediated iodination of Tg to form T4,T3 within the thyroid gland ( - ) TPO-mediated iodination of Tg to form T4,T3 within the thyroid gland PTU (but not methimazole ) blocks peripheral T4 PTU (but not methimazole ) blocks peripheral T4 T3 conversion T3 conversion both drugs may have immunosuppressive effects that may be responsible both drugs may have immunosuppressive effects that may be responsible

for the remission from the disease that some patients have after 1-2 years for the remission from the disease that some patients have after 1-2 years of treatment of treatment

THIONAMIDE CLASSTHIONAMIDE CLASS I. I. THIOURACIL DERIVATES THIOURACIL DERIVATES

METYLTHIOURACIL (50 mg/tb)METYLTHIOURACIL (50 mg/tb) PROPYLTHIOURACIL (PTU)(50 PROPYLTHIOURACIL (PTU)(50 mgmg/tb) /tb)

II. II. IMIDAZOLE DERIVATESIMIDAZOLE DERIVATES TIAMAZOLE (THYROZOLTIAMAZOLE (THYROZOL) 5) 5mgmg/tb/tb

CARBIMAZOLE 5mg/tbCARBIMAZOLE 5mg/tb

Initial dose - 6-12 tb/day ( 30-60 mg/ day of thyrozole) Initial dose - 6-12 tb/day ( 30-60 mg/ day of thyrozole) Maintenance dose- 1-3 tb/dayMaintenance dose- 1-3 tb/day SESE : rash, agranulocytosis(= indication for discontinuing the : rash, agranulocytosis(= indication for discontinuing the

medication), cholestatic jaundice with tiamazole and hepatocellular medication), cholestatic jaundice with tiamazole and hepatocellular toxicity with PTU , drug-induced hypothyroidism with an toxicity with PTU , drug-induced hypothyroidism with an ↑ of goiter( ← ↑ of goiter( ← ↑ of TSH secretion)↑ of TSH secretion) adding T4 supplements to prevent the patient adding T4 supplements to prevent the patient from becoming hypothyroid from becoming hypothyroid

TREATMENT OF HYPERTHYROIDISMTREATMENT OF HYPERTHYROIDISM

Surgical treatmentSurgical treatment Indications:Indications: Postdrug relapse of Graves’ disease Postdrug relapse of Graves’ disease Very large, compressive glands or multinodular goitersVery large, compressive glands or multinodular goiters Toxic adenoma in youthToxic adenoma in youth Patients who are allergic to or noncompliant with ATSPatients who are allergic to or noncompliant with ATS

subtotal or total thyroidectomysubtotal or total thyroidectomy The patient is prepared with ATS until euthyroid ( about 6 weeks); The patient is prepared with ATS until euthyroid ( about 6 weeks);

in addition, starting 2 weeks before the day of operation, in addition, starting 2 weeks before the day of operation, saturated solution of potassium iodide (SSKI) or Lugol’s solution saturated solution of potassium iodide (SSKI) or Lugol’s solution (3* 3drops daily (3* 3drops daily → 3* 15 drops/day ) is added→ 3* 15 drops/day ) is added will diminish the will diminish the hyperplasia and hypervascularity of the gland (the gland usually hyperplasia and hypervascularity of the gland (the gland usually becomes firm) and simplify surgery becomes firm) and simplify surgery

Complications of surgeryComplications of surgery: hypothyroidism, hypoparathyroidism, : hypothyroidism, hypoparathyroidism, reccurent laryngeal nerve injury reccurent laryngeal nerve injury

TREATMENT OF HYPERTHYROIDISMTREATMENT OF HYPERTHYROIDISM Radioactive iodine therapyRadioactive iodine therapy IndicationsIndications:: Toxic adenoma, toxic multinodular goiter Toxic adenoma, toxic multinodular goiter Allergy to or nonresponse to ATSAllergy to or nonresponse to ATS Contraindications to surgeryContraindications to surgery

3-10 mCi 131I 3-10 mCi 131I Following the administration of radioactive iodine (which typically is giving Following the administration of radioactive iodine (which typically is giving

orally as a single capsule) the gland will shrink and the patient will usually orally as a single capsule) the gland will shrink and the patient will usually become euthyroid over a period of 2-6 months become euthyroid over a period of 2-6 months

SE :SE : HypothyroidismHypothyroidism is the almost inevitable complication of radioactive iodine is the almost inevitable complication of radioactive iodine

therapy ( > 80%)therapy ( > 80%) Severe Grave’s eye disease is a contraindication to radioiodine therapy; Severe Grave’s eye disease is a contraindication to radioiodine therapy;

several prospective studies have shown that that radioiodine can several prospective studies have shown that that radioiodine can exacerbate eye problemsexacerbate eye problems when they are severe at baseline; however, when they are severe at baseline; however, potential worsening can be prevented by administration of prednisone 40-potential worsening can be prevented by administration of prednisone 40-60mg/day for 1-2 months (gradually tapering the dose) following the 60mg/day for 1-2 months (gradually tapering the dose) following the radioiodine treatment radioiodine treatment

Treatment of Treatment of hyperthyroidism hyperthyroidism

Other medical measuresOther medical measures RestRest Beta-adrenergic blocking agents : propranolol Beta-adrenergic blocking agents : propranolol 10-40mgevery 6 hours or longer acting beta-10-40mgevery 6 hours or longer acting beta-

blockers : metoprolol, atenolol control many blockers : metoprolol, atenolol control many adrenergic symptoms, tachycardia, adrenergic symptoms, tachycardia, hypertension, FAhypertension, FA

SedativesSedatives multivitaminsmultivitamins

Treatment of infiltrative orbitopathyTreatment of infiltrative orbitopathy Symptomatic treatmentSymptomatic treatment : ( useful mainly in mild forms) : ( useful mainly in mild forms)

dark glasses ( for those with photophobia, sensitivity to dark glasses ( for those with photophobia, sensitivity to wind or cold air), artificial tearswind or cold air), artificial tears

GlucocorticoidsGlucocorticoids : : prednisone prednisone 50-60mg/day, tapering 50-60mg/day, tapering the dose 10mg every 2 weeksthe dose 10mg every 2 weeks

intravenous methylprednisolone pulse intravenous methylprednisolone pulse therapytherapy 1g/day for 3 days- in severe cases ( the 1g/day for 3 days- in severe cases ( the advantage of fewer SE than high doses of prednisone)advantage of fewer SE than high doses of prednisone)

External radiationExternal radiation to the retrobulbar area to the retrobulbar area - The dosage is usually: 1000 cGy/ orbit in 10 fractions The dosage is usually: 1000 cGy/ orbit in 10 fractions

given over a period of 10 days given over a period of 10 days - → → if corticosteroid therapy is not effective or if corticosteroid therapy is not effective or

contraindicatedcontraindicatedThe best results are obtained by combining these 2 The best results are obtained by combining these 2

therapies ( glucocorticoids + external x-ray therapy)therapies ( glucocorticoids + external x-ray therapy) Surgical orbital decompressionSurgical orbital decompression can be used in very can be used in very

severe cases when vision is threatened severe cases when vision is threatened

HYPOTHYROIDISMHYPOTHYROIDISM

HypothyroidismHypothyroidism = a clinical syndrome resulting from a = a clinical syndrome resulting from a

deficiency of TH, which in turn results in a deficiency of TH, which in turn results in a generalized slowing down of metabolic generalized slowing down of metabolic processes processes

Classification:Classification: I – according to etiology;I – according to etiology;a)a) Primary (thyroid failure)-by far the most Primary (thyroid failure)-by far the most

commoncommonb)b) Secondary (due to pituitary TSH deficiency)Secondary (due to pituitary TSH deficiency)c)c) Tertiary (due to hypotalamic deficiency of Tertiary (due to hypotalamic deficiency of

TRH)TRH)d)d) Peripheral resistance to the action of THPeripheral resistance to the action of THII – according to the presence of goiterII – according to the presence of goiter Hypothyroidism –with goiterHypothyroidism –with goiter - without goiter - without goiter

Etiology of primary hypothyroidismEtiology of primary hypothyroidism Primary hypothyroidism with goiterPrimary hypothyroidism with goiter

1. 1. CONGENITALCONGENITAL Inherited defects in hormone biosynthesis (thyroid dyshormonogenesis) (e.g. Inherited defects in hormone biosynthesis (thyroid dyshormonogenesis) (e.g.

Pendred sdr = a defect in iodine organification+ sensory nerve deafnes)Pendred sdr = a defect in iodine organification+ sensory nerve deafnes) Endemic cretinismEndemic cretinism2. 2. ACQUIRED ACQUIRED Hashimoto’s thyroiditis=by far the most common causeHashimoto’s thyroiditis=by far the most common cause Iodine deficiency (endemic goiter)Iodine deficiency (endemic goiter) Excessive iodide intake (radiocontrast dye, amiodarone)Excessive iodide intake (radiocontrast dye, amiodarone) Cytokines: interferon alfa (used to treat hepatitis C) Cytokines: interferon alfa (used to treat hepatitis C)

Primary hypothyroidism (atrophicPrimary hypothyroidism (atrophic)) 1. 1. CONGENITALCONGENITAL Thyroid agenesiaThyroid agenesia Ectopic thyroid( lingual thyroid)-functions poorly ( Ectopic thyroid( lingual thyroid)-functions poorly ( absence of thyroid tissue or its absence of thyroid tissue or its

ectopic location can be ascertained by scintiscanning!)ectopic location can be ascertained by scintiscanning!) 2. 2. ACQUIREDACQUIRED Hashimoto’s diseaseHashimoto’s disease Postablative due to 131 I (radioactive iodine therapy), surgery Postablative due to 131 I (radioactive iodine therapy), surgery Transient (Post-thyroiditis ) hypothyroidismTransient (Post-thyroiditis ) hypothyroidism

Subacute thyroiditisSubacute thyroiditis Postpartum, silent thyroiditisPostpartum, silent thyroiditis

Hypothyroidism- pathogenesisHypothyroidism- pathogenesis

TH deficit in TH deficit in infants and childreninfants and children results in marked results in marked slowing of growth and development, with serious slowing of growth and development, with serious permanent consequences, including mental retardation, permanent consequences, including mental retardation, when it occurs in infancy. Hypothyrodism with onset in when it occurs in infancy. Hypothyrodism with onset in adulthoodadulthood a generalized a generalized ↓in metabolism, with slowed ↓in metabolism, with slowed heart rate, diminished oxygen consumption, and heart rate, diminished oxygen consumption, and deposition of GAG in intracellular spaces, deposition of GAG in intracellular spaces, particularly in skin, heart muscle and striated particularly in skin, heart muscle and striated muscle, producing in extreme cases the clinical muscle, producing in extreme cases the clinical picture of myxedema. picture of myxedema.

Clinical featuresClinical features Insidious onsetInsidious onset The common features of moderate- severe hypothyroidism include:The common features of moderate- severe hypothyroidism include:

fatigabilityfatigability Skin and appendagesSkin and appendages: cool, rough, dry, pale skin: cool, rough, dry, pale skin;; cold sensitivity ; cold sensitivity ;

puffy face, hands and feet( puffy face, hands and feet( ←non-pitting edema)→ ”pale moon-like ←non-pitting edema)→ ”pale moon-like face” or “”toad-like face”; reduced conversion of carotene to vit A face” or “”toad-like face”; reduced conversion of carotene to vit A may give the skin a yellowish color; macroglossia ;large lipsmay give the skin a yellowish color; macroglossia ;large lips

head and body hair is dry and brittle and tends to fall out; hair may head and body hair is dry and brittle and tends to fall out; hair may be lost from the temporal aspects of the eyebrows=Herthoge’s sign; be lost from the temporal aspects of the eyebrows=Herthoge’s sign; the nails are brittle and grows slolythe nails are brittle and grows sloly

Digestive manifestationsDigestive manifestations Constipation, Constipation, ↓↓appetite, appetite,

Modest gain in weight (generally <10-20pounds)Modest gain in weight (generally <10-20pounds) Neuromuscular systemNeuromuscular system: Numbness and tingling of the extremities, : Numbness and tingling of the extremities,

muscle cramps, muscle weaknessmuscle cramps, muscle weakness Central and peripheral NSCentral and peripheral NS :all intelectual functions, including speech, :all intelectual functions, including speech,

are slowed; loss of initiative, memory deficits, lethargy and are slowed; loss of initiative, memory deficits, lethargy and somnolence are present; psychiatric disorders are common: somnolence are present; psychiatric disorders are common: depression or even agitation (“myxedema madness”) ; slow reflexesdepression or even agitation (“myxedema madness”) ; slow reflexes

Hearing lossHearing loss Thick, slurred speech, hoarsenessThick, slurred speech, hoarseness

Clinical featuresClinical features Reproductive functionReproductive function

Excessive menstrual bleeding , menorrhagia , failure of ovulation, Excessive menstrual bleeding , menorrhagia , failure of ovulation, ↓fertility↓fertility, galactorrhea , galactorrhea

↓↓libido, impotence, oligospermialibido, impotence, oligospermia

Cardiovascular signsCardiovascular signs→ → impaired ventricular contraction, bradycardia, ↑peripheral impaired ventricular contraction, bradycardia, ↑peripheral

resistance resulting in ↓cardiac output, narrowing of pulse resistance resulting in ↓cardiac output, narrowing of pulse pressurepressure

convergent BP formula (TAd=90-100mm Hg ←↑ systemic vascular convergent BP formula (TAd=90-100mm Hg ←↑ systemic vascular resistance)resistance) ; heart sounds are diminished in intensity ; heart sounds are diminished in intensity

Cardiac enlargement Cardiac enlargement ← interstitial edema, left ventricular dilatation, ← interstitial edema, left ventricular dilatation, (nonhemodynamically significant) pericardial effusion(nonhemodynamically significant) pericardial effusion

Pulmonary functionPulmonary function dyspneadyspnea obstructive sleep apneaobstructive sleep apnea

Renal functionRenal function-is impaired , with ↓ glomerular filtration rate and impaired ability -is impaired , with ↓ glomerular filtration rate and impaired ability

to excrete a water load to excrete a water load

Clinical featuresClinical features

Hashimoto’s thyroiditis may associate other autoimmune disordersHashimoto’s thyroiditis may associate other autoimmune disorders EndocrineEndocrine

CSRI (with adrenal autoantibodies), gonadal CSRI (with adrenal autoantibodies), gonadal insufficiency , DM type I (with islet cell antibodies0 insufficiency , DM type I (with islet cell antibodies0

Non-endocrineNon-endocrine vitiligo, pernicious anemia, alopecia vitiligo, pernicious anemia, alopecia =Schmidt’s syndrome=Schmidt’s syndromeThese conditions are part of what has been termed These conditions are part of what has been termed

“autoimmune polyglandular syndrome” “autoimmune polyglandular syndrome”

HYPOTHYROIDISM-DiagnosisHYPOTHYROIDISM-Diagnosis 1. 1. Hormonal determinationsHormonal determinations

Basal Basal Primary H – the combination of TSHPrimary H – the combination of TSH , T3 , T3, T4 , T4

(FT4)(FT4)=diagnostic =diagnostic Central H – TSHCentral H – TSH/low-normal, T3/low-normal, T3, T4(FT4), T4(FT4) anti-Tg antibodies, anti-TPO antibodies =anti-Tg antibodies, anti-TPO antibodies =↑ in Hashimoto’s ↑ in Hashimoto’s

thyroiditisthyroiditis Dynamic tests – TRH testDynamic tests – TRH test →in diagnosis of Central H for assessment →in diagnosis of Central H for assessment

of TSH pituitary reserve ( give protirelin (TRH) 200-400 µg iv; blood of TSH pituitary reserve ( give protirelin (TRH) 200-400 µg iv; blood for determination of plasma TSH is obtained at 0’ and 60’)for determination of plasma TSH is obtained at 0’ and 60’)

normal response: ↑TSH > 2 * baseline valuenormal response: ↑TSH > 2 * baseline value In central H – no response/ subnormal responseIn central H – no response/ subnormal response In primary H – an exaggerate TSH responseIn primary H – an exaggerate TSH response

2. 2. Imagistic findingsImagistic findings Thyroid ultrasonography – thyroid volume: normal, Thyroid ultrasonography – thyroid volume: normal, ↑, ↓; an ↑, ↓; an

hypoechogen aspect in Hashimoto’s thyroiditis is usually presenthypoechogen aspect in Hashimoto’s thyroiditis is usually present RAIU + Thyroid scintigraphy – usually employed for assessing inherited RAIU + Thyroid scintigraphy – usually employed for assessing inherited

defects in hormone biosynthesis or thyroid agenesia, ectopic thyroiddefects in hormone biosynthesis or thyroid agenesia, ectopic thyroid

HYPOTHYROIDISM-DiagnosisHYPOTHYROIDISM-Diagnosis Serum cholesterol and tryglicerides Serum cholesterol and tryglicerides Anemia: usually –mild normocytic, normochromic anemia Anemia: usually –mild normocytic, normochromic anemia ← impaired ← impaired

hemoglobin synthesis/hemoglobin synthesis/ macrocytic anemia macrocytic anemia←folate deficiency from ←folate deficiency from impaired intestinal absorption of folic acid, pernicious anemia, with vit impaired intestinal absorption of folic acid, pernicious anemia, with vit B12-deficient megaloblastic anemia/ microcytic, hypochromic anemia← B12-deficient megaloblastic anemia/ microcytic, hypochromic anemia← increased iron loss with menorrhagia, defective absorption of iron increased iron loss with menorrhagia, defective absorption of iron resulting from achlorhydria resulting from achlorhydria

Creatine phosphokinase (CPK), AST, LDH Creatine phosphokinase (CPK), AST, LDH ← abnormal muscle membranes ← abnormal muscle membranes (the source is skeletal muscle)(the source is skeletal muscle)

ECGECG Low-voltage of QRS complexes and P and Twaves (with improvement in Low-voltage of QRS complexes and P and Twaves (with improvement in

response to thearpy)response to thearpy) Prolongation of the QT and PR intervalsProlongation of the QT and PR intervals Sinus bradycardia; rarely complete heart blockSinus bradycardia; rarely complete heart block alterations of the ST segment and flattened or inverted Twavesalterations of the ST segment and flattened or inverted Twaves

Thoracic X-rayThoracic X-ray Cardiac enlargementCardiac enlargement

EchocardiographyEchocardiography Effusion into the pericardial sacEffusion into the pericardial sac

ComplicationsComplications 1.Mixedema coma1.Mixedema coma: the end stage of untreated hypothyroidism; it is characterized by : the end stage of untreated hypothyroidism; it is characterized by

progressive weakness, stupor, hypothermia (T< 35 progressive weakness, stupor, hypothermia (T< 35 ºC), hypoglycemia, hyponatremia, ºC), hypoglycemia, hyponatremia, hypoventilation and it may ultimately result in shock and deathhypoventilation and it may ultimately result in shock and death

2. 2. Mixedema cardiomyopathyMixedema cardiomyopathy → congestive heart failure→ congestive heart failure ECG – bradycardia, pECG – bradycardia, prolongation of the QT and PR intervals,rolongation of the QT and PR intervals, AV block AV block Echocardiography – cardiac hypertrophy, then ventricular enlargement with Echocardiography – cardiac hypertrophy, then ventricular enlargement with EF EF

3. 3. Mixedema pericarditisMixedema pericarditis ( pericardial effusion is rarely of sufficient magnitude to cause ( pericardial effusion is rarely of sufficient magnitude to cause tamponade)tamponade)

4. 4. Coronary artery disease-Coronary artery disease- likely related to likely related to ↑ levels of total cholesterol, LDL-↑ levels of total cholesterol, LDL-cholesterolcholesterol

5. 5. MyopathyMyopathy

6. In newborn infants – impairment of linear growth results in 6. In newborn infants – impairment of linear growth results in dwarfismdwarfism with the limbs with the limbs disproportionately short in relation to the trunk +disproportionately short in relation to the trunk +retardation of mental and physical retardation of mental and physical developmentdevelopment ! The importance of routine screening of newborns for TSH or T4 because ! The importance of routine screening of newborns for TSH or T4 because early diagnosis can prevent permanent mental retardation ( a drop of blood obtained by early diagnosis can prevent permanent mental retardation ( a drop of blood obtained by heel stick 24-48h after birth is placed on filter paper; a serum T4< 6heel stick 24-48h after birth is placed on filter paper; a serum T4< 6µg ‘dl or a serum µg ‘dl or a serum TSH>25 mU/l is suggestive of neonatal hypothyroidism; the diagnosis can then be TSH>25 mU/l is suggestive of neonatal hypothyroidism; the diagnosis can then be confirmed by repeat testing and radiologic evidence of retarded bone age)confirmed by repeat testing and radiologic evidence of retarded bone age)

Treatment of HypothyroidismTreatment of Hypothyroidism = replacement treatment- with T4, which is available in pure forms, and is = replacement treatment- with T4, which is available in pure forms, and is

stable and inexpensivestable and inexpensive DrugsDrugs

L-T4 (Levothyroxine, Euthyrox)L-T4 (Levothyroxine, Euthyrox) 50-100(200)microg/day with a mean 50-100(200)microg/day with a mean of 125 of 125 µg/day ( because T4 is converted to T3 in peripheral tissues, µg/day ( because T4 is converted to T3 in peripheral tissues, both hormone become available even though only one is administered); both hormone become available even though only one is administered); the T1/2 of T4 is about 7days, so it need be given only once daily; the T1/2 of T4 is about 7days, so it need be given only once daily; before breakfast for an optimal absorptionbefore breakfast for an optimal absorption

( L-T4/T3 (NOVOTHYRAL) 100 LT4 + 20T3/tb)( L-T4/T3 (NOVOTHYRAL) 100 LT4 + 20T3/tb) Considerations:Considerations:

Usually for life, with the exception of transient hypothyroidism (e.g. Usually for life, with the exception of transient hypothyroidism (e.g. subacute thyroiditis); subacute thyroiditis);

The initial dose of levothyroxine prescribed depends on the degree of The initial dose of levothyroxine prescribed depends on the degree of hypothyroidism, the age and general health of the patienthypothyroidism, the age and general health of the patient

in most patients (young or middle- agedin most patients (young or middle- aged and otherwise healthy with no and otherwise healthy with no associated cardiovascular or other abnormalities ), one can begin associated cardiovascular or other abnormalities ), one can begin treatment with the full estimated dose requirementtreatment with the full estimated dose requirement

in older patients or patients with underlying heart diseasein older patients or patients with underlying heart disease, it is best to , it is best to start with a low dose of T4 (eg 25 start with a low dose of T4 (eg 25 µg/day) and increase the dose µg/day) and increase the dose slowly( at 1-2 week intervals) until the full dose required with careful slowly( at 1-2 week intervals) until the full dose required with careful clinical and laboratory evaluation ; association of beta-adrenergic clinical and laboratory evaluation ; association of beta-adrenergic blocking agents is helpfulblocking agents is helpful

Treatment of HypothyroidismTreatment of Hypothyroidism

The goal in the patient with The goal in the patient with primary primary hypothyroidismhypothyroidism is to return serum is to return serum TSH TSH concentrations to normal; the serum TSH should concentrations to normal; the serum TSH should be evaluated be evaluated 6 weeks after a theoretically completed 6 weeks after a theoretically completed replacement dose has been institutedreplacement dose has been instituted

In patients with In patients with central hypothyroidismcentral hypothyroidism serum serum TSH is not a reliable index of adequate TSH is not a reliable index of adequate replacement and the replacement and the serum FT4serum FT4 should be should be restored to a concentration in the upper half of the restored to a concentration in the upper half of the normal range. !such patients should also be normal range. !such patients should also be evaluated and treated for glucocorticoid deficiency evaluated and treated for glucocorticoid deficiency before institution of thyroid replacementbefore institution of thyroid replacement

Monitoring replacement therapy: initially at 6-Monitoring replacement therapy: initially at 6-8weeks, then 2*/year 8weeks, then 2*/year