Endocrine Disorders in Egypt PDF

\ \ \ ; Endocrine Disor ers I I I I Theoretical / / I...

\ \ \ ; Endocrine Disor ers I I I I Theoretical / / I I I I S9 [5th ye r] - 2023 I \ \ \ \ y \ ' ' ' EPIDEMIOLOGY OF COMMON ENDOCRINAL DISORDERS IN EGYPT Diabetes Mellitus ,.. - Hypothyroidism 4 Short Stature 6 Chapter 1: The pituitary gland Anatomy and Physiology 10 Growth Hormone Deficiency 14 Growth and Development 17 Short Stature 24 Hypopituitarism 28 Growth Hormone Hypersecretion: ► Gigantism 36 ► Acromegaly 37 Pituitary Tumours: 43 ► Prolactinoma 45 Visual Disturbances In Pituitary Tumors: 48 ► Pituitary Adenomas ( Chromophobe adenoma) 52 ) Posterior Pituitary: 55 ► Diabetes lnsipidus [ DI] 57 ► SIADH 63  Chapter 2: The Thyroid Gland Anatomy and Evaluation of Thyroid Function 66 Thyrotoxicosis: 72 I\:- Graves' Disease Basedow Disease 11 73 --- ► II "=' J Hypothyroidism Causes 84 Adult Hypothyroidism [ myxedema] 85 - , Cl - i' Congenital Hypothyroidism 90 "n. ' ' '. Congenital Anomalies of Thyroid Gland: I - ,. Thyroglossal cyst "- 96 ,. Thyroglossal Fistula 98 - \t ! ► Ectopic Thyroid 99 ► Congenital aplasia or hypoplasia 99 Thyroiditis: f').r:--'J ► Subacute Thyroiditis ( De Quervain ) 100 - lo-.r.... J :- ► Chronic Lymphocytic Thyroiditis ( Hashimoto's Thyroiditis ) 101 Goitre: 102 ",. Simple Goitre 103 1 - ► Retrosternal Goitre 109 - \t ! Tumours of The Thyroid 112 Solitary Thyroid Nodule 121 Thyroidectomies 123 Thyroid Eye Disease: ( Graves Ophthalmopathy) 129 Idiopathic Orbital Inflammatory Disease ( IOID) 134 -.. -' Orbital Myositis 135 j) Indirect Carotid Cavernous Fistula 135 Optic Nerve Sheath Meningioma 136 Optic Nerve Glioma 138  Chapter 3: Parathyroid Glands Physiological Background on Calcium Regulation 140.., 141... Hypoparathyroidism '-' Hyperparathyroidism (HPT) 147 Chapter 4: The Adrenal Gland Anatomy & function of adrenal gland 158 Cushing's Syndrome 159 Addison's Disease 166 Congenital Adrenal Hyperplasia (CAH) 173 Adrenal Tumours 176 Chapter 5: Reproductive Endocrinology Gynecomastia 182 d',p Hirsutism 186 Polycystic Ovarian Syndrome 188 - I , Q - r Puberty 190 -.. ·" '  Chapter 6: Pancreas Diabetes Mellitus 203 I- , Diabetes Treatment 211 Complication of Diabetes 224 Diabetic Retinopathy (DR) 251 Type-1 Diabetes Mellitus ( TlD ): 260 I Q.- ).' Rn ► Diabetic Ketoacidosis ( DKA) 263 Diabetes National Screening Guidelines 269., Hypoglycaemia 278. Neonatal Hypoglycemia 284.. ·"' I Q - r A Pancreatic Tumours 288 Lipid Disorders 289. - Inborn Errors of Metabolism 293 IQ --. ' ·., Chapter 7: Clinical Case Sheets Approach To a Case of Short Stature 299 Acromegaly Case Sheet 302 Hypothyroidism Case Sheet 304 Hyperthyroidism Case Sheet 306 Evaluation of A Case of Proptosis 308 Diabetes Mellitus Case Sheet 313.. EPIDEMIOLOGY OF COMMON ENDOCRINAL.. DISORDERS IN EGYPT...... Diabetes Mellitus.... Magnitude & burden in Egypt...... ! Magnitude: - The prevalence of type 2 diabetes {T2D) in Egypt is around 18.4% of all adults aged.. 20 to 79. - Egypt as the ninth leading country in the world for the number of patients with T2D ( The International Diabetes Federation ) ! Burden: - Diabetes Mellitus {DM} imposes a huge economic burden on:.. [ 1. individuals 2. families 3. health care systems 4. countries J - The total cost of Diabetes was calculated to be (EGP 25.2 billion) equivalent to ( USO 3.5.. billion ).... - The highest burden on both governmental and private sectors due to the management...... of complications costs. Risk factors...... 1. Age:... in young age: IDDM is common... In old age: NIDDM & glucose intolerance are common..., 2. Sex: both sexes are equal.... 3. Obesity: 80% of NIDDM are obese.. 4. Genetic or familial tendency:.. the incidence of diabetes increases in children whose parents have Diabetes. 5. Autoimmunity to Islet cells of the pancreas.... 1 M.- _________ -.. Scanned with CamScanner  ,J 6. Stress: 1- trauma 2- operation 3- depression 4- anxiety 5- severe infection 7. Inflammation of pancreas by:..) 1) viruses: ( mumps, coxsackie, enterovlrus )..a 2) cancer pancreas - 3) after pancreatectomy - 8. Drugs: 1- diuretics 2- corticosteroids 3- contraceptive pills. 9. Hormone disturbance: - increased thyroid & growth hormone levels with Insulin-antagonistic action - 10. Chronic H patitis C Infection: ,.a The prevalence of T2D among patients with HCV is 13%: 33%. 11. Pesticide exposure: exposure to agricultural pesticides. 12. Smoking: smoking is directly linked to increased incidence of microvascular and macrovascular diseases in patients with Diabetes. Prevention -a _, O) Primordial prevention: _. - The development of prevention programs for Diabetes based on the elimination of... environmental risk factors are possible, e.g., high taxes on the cigarettes industry _. 1) Primary prevention:... 1. Prevent predisposing factors as [ obesity, smoking, sedentary life, infections ]. -, 2. Vaccination against mumps. _., 3. Care in using drugs for long time. _, 4. Pre-marital counseling is recommended. 5. Health education for.....ii ► physical activity ,,,,it increased consumption of vegetables & fruits... ► decreased intake of refined sugars, sweets and fat.... -® 2 ► - -t Scanned with CamScanner  ' 2) Secondary prevention: ,.. 1-­... 1. Early case finding: - by screening tests for glucose intolerance, or during checkup for at risk groups like those with: ► familial tendency ;. obese persons ;. those with age over 40 years IM... ;. pregnant females ;.. patients using drugs for long time - Presidentiable's initiative 100 Million Healthy Lives Initiative was launched in October 2018 for the early detection of: 1) Hepatitis C virus (HCV)... 2) non-communicable diseases (NCDs) [ Diabetes, high blood pressure, obesity ]... for more than 50 million Egyptian citizens... - The Initiative follows up on patients and provides treatment via treatment centers. I..... 2. Proper management of diagnosed cases... 3. health educatJon: for adherence to diet & treatment to prevent complications... diet regimen is an important line of treatment.. I.... 4. Frequent check up on retina & renal functions every 6 months,.. 3) Tertiary prevention: to..... 1. limit complications.. 2. reduce suffering... 3. rehabilitation..... 4) Quaternary prevention: to avoid..... 1. unnecessary screening.. 2. inappropriate investigations,.. 3. overdiagnosis.. 4. unwarranted therapeutic measures _______________ ----- --- -._ 3 Scanned with CamScanner ,,,,..; Hypothyroidism....... Magnitude & burden in Egypt -ii ! Magnitude: -- - Worldwide, the incidence of individuals with thyroid dysfunction is increasing and _. represents approximately 30- 40% of the patients seen in an endocrine clinic. __. - Hypothyroidism affects up to 5% of the general population, with a further estimated.... 5% undiagnosed. ,,.,f - up to one-third of patients are not receiving adequate treatment. _. ! Burden:..... - The undiagnosed thyroid dysfunction may adversely affect metabolic control and increase cardiovascular risk factors _,,j - Congenital hypothyroidism is one of the preventa,ble causes of mental retardation....... - Hypothyroidism is associated with... ,.,. 1. decreased quality of life 2. increased sick leave days 3. even increased mortality _. - The economic impact of undiagnosed, untreated, or undertreated hypothyroidism may __. be significant. __. Risk Factors: One is at an Increased risk if he/she:... 1. is a woman.... 2. is aged older than 60 ,,,,, 3. Have a family history of thyroid disease 4. Have an autoimmune disease, such as ( type 1 diabetes or celiac disease ) _.ii --' 5. Have been treated with ( radioactive iodine or anti- thyroid medications )..., 6. Received radiation to the neck or upper chest -' 7. · Have had thyroid surgery ( partial thyroldectomy ).... 8. Have been pregnant or delivered a baby within the past six months.... ® 4..., Scanned with CamScanner...... Prevention... 0) Primordial prevention:... - Prevention of iodine deficiency disorders by adequate iodine nutrition: Salt lodization.. Salt iodization is the simplest, cheapest, and most effective means of providing.. optimum iodine nutrition. 1) Primary prevention: Preventing common environmental exposures such as: [ perchlorate, thiocyanate, and nitrate ( endocrine disruptors } ]._ 2) Secondary prevention:... 1. Screening: 91111 a) Screening of People who may have a higher risk of thyroid problems b) Screening of newborns for hypothyroidism: ► A heel-prick blood test at S days of age is done for intake of refined all newborns... The Egyptian Ministry of Health and Population (MOHP} endorsed the screening.. program for congenital hypothyroidism (CH} 1:1sing TSH assay method... If the TSH is high on the heel-prick blood test, it suggests that the thyroid.. hormone is low, a small blood sample taken from a vein to confirm the diagnosis.. If the baby tests positive, Treatment with levothyroxine should be started.. without delay.. 2. Diet:.. No specific diet is recommended for hypothyroidism.... Individuals should follow a varied, well- balanced diet that is not high in fat or Na..... Autoimmune Hashimoto's patients may benefit from following a gluten-free diet... 3) Tertiary prevention: Prevention of complications and rehabilitation...... 4) Quaternary prevention: identify patient at risk of overmedicalization... - Easy availability and accessibility of thyroid function tests has led to an increase In the.. number of diagnosed hypothyroid and hyperthyroid cases.. s.... Scanned with CamScanner  ,J.a -- Short Stature -..,.. Magnitude & burden in Egypt ! Magnitude: - Globally In 2016, 22.9% or 154.8 million children under five years of age suffered from _, child stunting. _., - In Egypt, the overall prevalence of short stature constituted 17%... _, : Burden: _. - Stunted children with deficiencies of iodine & iron may suffer irreversible brain damage.... - They have:.... 1) a shorter adult height 2) lower attained schooling 3) reduced adult income... 4) higher susceptibility to chronic diseases in adulthood..... - Stunted and wasted children also have a higher mortality risk..-1 - Stunting also has a transgenerational effect as mothers who were themselves stunted... as children tend to have offspring with stunted growth..... - WHO declared Stunting a global health priority and called for a 40% reduction in the -­ number of stunted children by 2025.ii.... Risk Factors... -, 1. growth hormone deficiency (GHD) 2. hypothyroidism 3. celiac disease 4. Turner syndrome, other genetic syndromes. -" 5. Maternal malnutrition.... 6. Diarrhea & parasitic infestations. _. Other causes include: 7. renal, hepatic, and gastrointestinal diseases _, Normal variants such as: 8.... 1) familial shor:t stature 2) idiopathic short stature...... 3) constitutional delay of growth & puberty...., ® 6 -t _________ ________ __ __ _________----1 Scanned with CamScanner.. Prevention: 0) Primordial prevention:... 1. formulation of a nutrition policy and overall long term planning to improve... production and supplies of food, ensure its equitable distribution and.. programs to increase the purchasing power of people.. 2. various welfare measures conducted by the government target pregnant women,.. infants, preschool and school children by nutritional supplementations.... &a 1) Primary prevention: a. Adequate nutrition:... 1. Give exclusive Breast feeding For 6 Months in Babies.. 2. Fulfill Nutritional Needs Since Pregnancy.. 3. pregnant women are advised to consume healthy and nutritious foods or supplements recommended by doctors... 4. Zinc is essential for adequate growth, and supplements have been shown to.. increase intrauterine femur length and to prevent stunting... b. Growth monitoring: parents are encouraged to monitor height and weight of their.. child condition regularly... c. Maintain Environmental Cleanliness... d. Treatment of chronic & parasitic diseases... 2) Secondary prevention:........ a. Screening programs for early detection of stunting:.. - In Egypt, a presidential Initiative was held to screen primary school children for stunting targeting 15 million children in schools... b. Early management of stunted children:.. - Treatment for short stature depends on the cause..... 7 ®ij... Scanned with CamScanner ,.,... c. Patient education: in the counseling of patients and family members to.... 1. improve the quality of life.-4).., 2. help individuals deal with the effects of bullying, social isolation, and stress associated with short stature llllf 3) Tertiary prevention: Prevention of complications and rehabilitation..... 4) Quaternary prevention:... - Action taken to identify patient at risk of over medicalization to: --- 1. protect him from new medical invasion ,.., 2. suggest interventions ethically acceptable..... r...J 0.......-e _.............,.-., 8 Scanned with CamScanner  +o The pituitary gland 1. Anatomy & physiology 2. Growth hormone deficiency 3. Growth and development 4. Short stature 5. Hypopituitarism 6. Growth hormone hypersecretion 7. Pituitary tumours 8. Visual disturbances in pituitary tumors 9. Posterior pituitary a. Diabetes insipidus b. Syndrome of inappropriate adh secretion 9 L Scanned with CamScanner ,J..... ANATOMY & PHYSIOL0GY....., Anatomy.., - "" 1. Site & relations: Clrod... ==--- ,___ Pilutvy )... - Lies within sella turcica. I ,.,,..o'> 7 l?O t V e.,,_,,. r_......·__,,,..r::.,..., w 70 L,' 30 10 E IIO ,,., GO =f... - I -- --... 50 ?.:: !IO C: H ::o - ,o.,..0... :so I lO lb 2 :a 4 S G 7 e ? 10 11 U t> &4 15 IG "l7 te 19 ::0 A4)0(y-.-.) 25 Scanned with CamScanner..a.. B) Pathological:... 1. Nutrition & gastrointestinal conditions:.. 1) Malnutrition 2) Celiac disease 3) Inflammatory bowel disease... 2. Genetic and chromosomal disorders:... 1) Turner syndrome 2) Prader-Willi syndrome 3) Silver Russel syndrome...... 4} Noonan syndrome 5) Trisomy 21 6) Mucopolysacharidosis.... 7) Achondroplasia.... 3. Endocrine conditions: ( Bone age is delayed )... 1) Isolated growth hormone deficiency, Insulin growth factor 1 ( IGFl ) deficiency... ( Laron syndrome )..... 2) Hypoparathyroidism.... 3) Hypogonadlsm.... 4) Cushing syndrome... 5) Adrenal insufficiency.... 6) Hypothyroidism: congenital/ autoimmune thyroiditis.... 7) Metabolic bone disease: rickets, hypophosphatasia....... 8) Growth hormone deficiency: Panhypopituitarism e.g. craniopharyngioma ( rare but must be excluded )....... 4. Psychological deprivation: _.. - Disturbed chi Id-mother or family relation reduces growth hormone release...,.... 5. Severe systemic dise.ases in infancy and childhood.... ► Chronic diseases:... 1) chronic kidney disease 2) cystic fibrosis 3) liver cell failure.... 4) chronic neurological disorders 5) malabsorptlon 6) hemolytic anemia.... , Chronic Infections: e.g tuberculosis, bllharziasis........ 6. Medications: 1) Glucocorticoids 2) Inappropriate sex steroid exposure. @.... 26 Scanned with CamScanner C) Idiopathic Short Stature: - No endocrine or metabolic disorders. - Often normal growth velocity. - Height< - 2.2 5 SD mean for age. - Normal growth hormone stimulation test. Treatment: Depends on underlying aetiology... 1) Adequate nutrition and caloric intake, minerals and vitamins especially in patients with malnutrition. 2) Psychological support in maternal deprivation. 3) Adequate management of chronic illness. 4) Hormone replacement in children with GH deficiency: SC recombinant growth hormone, daily, before sleep. Response to growth hormone therapy is measured ( every 3-6 mo.) by Ht and occasional bone age measurement. 5) Other pituitary deficiencies should be treated e.g. L-thyroxine, Hydrocortisone. 27 Scanned with CamScanner ,-) _..a... HYPOPITUITARISM 1..il... Causes... 1. Infarction of pituitary:.-t... a) Postpartumnecrosis ( sheehan syndrome): I... - the most common cause. l... - The anterior pituitary is most susceptible to infarction in the post-partum period I ( P.P. Hge } because: _.. I 1) It Is enlarged during pregnancy without increase in blood supply.... 2) Its blood supply is mainly venous. b) Vascular disease: e.g. vasculitis, D.M..... I... 2. Infections & granuloma: T.B., syphilis, meningitis, sarcoidosis..... I... 3. Idiopathic ( congenital ): deficiency of one or all anterior pituitary hormones.... 4. Neoplastic: adenoma, craniopharyngioma, leukaemia, lymphoma, metastasis..... 5. Physical agents: radiation, surgery, head trauma..... 6. Miscellaneous: e.g. haemochromatosis, histiocytosis X.......... Clinical picture....... a) In childhood: _. 1. Pituitary dwarfism ( Levi - lorain syndrome ):.... 1) Proportionate dwarfism. 2) Childish facies...-9 _.. I 3) Later on, hypogonadism may appear ( with cryptorchidlsm in male)..... There is L GH "commonly idiopathic".-4... ® 28 ------------ ---------- j.... - Scanned with CamScanner 2. Frohlich 's syndrome ( dystrophia adiposo - genetalis ): l} Dwarfism... 2) hypogonadism.... 11 ). 3} Obesity ( in trunk, face sparing the extremities samboxa shaped obesity.... II... 4) Genu valgum. 5) Hypothalamic disturbances as [ 0.1., polyphagia, hypersomnia ].... It is commonly due to tumour or functional hypothalamic disturbance "idiopathic ".... 3. Laurance - Moon - Biedle syndrome:.. - Similar to Frohlich's syndrome +...... 1) Mental retardation 2) skull deformities. 3) Retinitis pigmentosa..................... b) In adults:.. 1. Panhypopituitarism ( Simmond's disease)... 2. Isolated hormone deficiency..... Clinical features.... A) l Prolactin ➔ failure of lactation... B) l Growth hormone ➔ silent, rarely leads to hypoglycaemia... 29 M:: Scanned with CamScanner  C) ! Gonadotrophic hormones:.. 1) Eunuchoid appearance: 1) Skin:... 1. Tall ( span > height ) 1. fine wrinkled, ,.. 2. Obese. 2. loss of 2ry sexual hair progeria II 11 "' 3. Prepubertal genitalia ( small, soft ,.. testicles ). 4. Absent facial, pubic & axillary hair. 2) Sexual manifestations: ctJ1: ! libido, impotence, ,.. testicular atrophy, oligospermia.... 2) Primary amenorrhea: 22 mm... 4. Joints X-ray: osteoarthritic changes..... 5. C.T. & MRI: for detection of pituitary tumours... X-ray chest can be done to exclude bronchial carcinoid as a cause of acromegaly ( paramalignant syndrome). 39 Scanned with CamScanner -...., I..,..., I.;, Tufting of the terminal phalanges Heel pad > 22 mm. I_. I I ( brush border ) 1-a...... ,_,j 1.J........ - - _............ I.... _. _. r-4...... I ,,,A ,,A ,,,A ® - - 40 Scanned with CamScanner  B) Visual field & ophthalmologic examinattion: 1. Bi-temporal Hemianopia 2. papilloedema, 3. optic atrophy 4. glaucoma "in sever casesn. C) Endocrinal: 1. G.H.: - t basal level " > 6 ng / ml" - Failure of G.H. suppression in response to oral glucose load (to< 2ng / ml } - IGF-1 levels are increased. 2. GH-RH: j in ectopic secretion from bronchial carcinoid 3. Measurement of PRL: which may be also secreted by tumor. 4. Measurement of TSH, ACTH, gonadotrophins (GN): to detect associated hypopituitarism. D) Investigation for metabolic effects: 1. j BMR. 2. Hyperglycaemia. 3. Hypercalcaemia. Serum Ca usually drops to normal after successful ttt of acromegaly, but if not indicates associated MEN I Treatment 1. Surgical ( ttt of choice):--+ rapid relief of symptoms. 2. Radiotherapy: - " Proton beam, heavy particles, supra voltage radiation, gamma knife radlosurgery" may require several years for a full therapeutic effects. - Indicated in: 1) small tumors 2) Post. operativ·e 3) C.I to surgery - Contra Indications: 1) large tumors 2) major visual field defect 3) GH > 50 ng/ ml. 41 ------------------ ------ ---- Scanned with CamScanner 3. Medical ttt: 1 a) Dopamine agonist: e.g. bromocriptine 1 1 1 - Indicated: when surgery is contraindicated especially for cases needing rapid relief of symptoms. - Dose: 15-30 mg/ day. Cabergoline is more useful - GH L , only in 10 - 40% of cases. - At present, It Is used as adjunctive therapy following surgery or radiotherapy. b) Somatostatin: - Not specific for GH. - Has to be given by infusion. c) Octreotide ( analogue of somatostatin ): - Has longer duration of action & is specific. - Can be given s.c. / 12 hrs. - A long acting depot form of octreotide [ Sandostatin LAR] ➔ monthly 1.M. inject. d) Pegvisomant: - GH receptor antagonist " Trovert " - J, IGF.I, but not size of tumour. - Successful ttt should restore serum GH to < 1 ng/ ml and IGF-1 to normal. - Follow up every 6 - 12 ms after surgery or radiotherapy for the possible development of other ant. Pit. hormone deficiency. Scanned with CamScanner  PITUITARY TUMOURS -- Incidence - Constitute about 15% of all intracranial tumours. - Types: 1. PRL producing tumours 35% 2. Non functioning tumours 30% 3. GH secreting tumours 20 % 4. Mixed PRL & GH secreting tumours 9% 5. TSH, LH, FSH, ACTH secreting tumours 6% - Clinical picture - A) Acute: Pituitary apoplexy B) Chronic: 1. Endocrine effects: a) Hyperpituitarism ( according to the hormone secreted ). b) Hypopituitarism. c) Associations: MEN I ( Pituitary, Pancreas, Parathyroid). 2. Mass effects: 1) Headache: bi-temporal - When the tumours enlarges: it erodes the clenoid process & escapes to the cranial cavity ➔ improval - Rare & late the tumor increases in size ➔ occipital headache + 1' ICT. 43 2. Superior extension: ► Chiasmal syndrome: ! visual acuity & bitemporal hemianopia. ► Hypothalamic syndrome: 1) D.I. 2) Disturbance of -+- thirst, temperature, appetite, sleep regulation. 3) SIADH 3. Lateral extension: 1) Cranial 3, 4, 6 & ophthalmic division of trigeminal n. impairment diplopia & facial pain. 2) Temporal lobe dysfunction. 4. Inferior extension: 1) Nasopharyngeal mass 2) C.S.F. rhinorrhea 5. Posterior extension: Bilateral pyramidal signs. Optic chiasm Internal carotid­.--CNIII/ 1.___.artery Pituitary / gland CN IV ,.-- ,-.. , -;... us·sln VI 44  PROLACTIN HYPERSECRETION '' Prolactinoma ,, - Physiology of Prolactin ( PRL) Hormone - ! Action: a) Breast milk production. b) Suppression of menstruation. ! Control: Nocturnal peak ( which is sleep related ). - Incidence: This is usually a microadenoma in @, macroadenoma in @ - - Clinical picture 1. Manifestations of sellar tumour: see before. 2. In females: ( j prolactin ii GnRH) a) Amenorrhea and/or galactorrhea. b) Hypoestrogenic symptoms: 1. ! Libido. 2. ! vaginal secretion. 3. Dyspareunia. 4. Osteoporosis. c) Hyperandrogenic manifestations: ( j PRL ➔ j adrenal androgens ) 1. Hirsutism 2. acne 3. In males: 1) ! libido & impotence. 2) Oligospermia & infertility. 3) Gynaecomastia "rare" 4. In both sexes: delayed puberty. 45  Investigations 1. Basal prolactin level: ► @ O - 25 ng / ml. ► (!} O - 20 ng / ml. 2. Plain X-ray, CT, MRI: for detection of pituitary tumours ( see later). D.D. of causes of hyper-prolactinaemia A) Physiological: 1. pregnancy 2. suckling - stress - stimulation of the nipple. B) Drugs: 1. Dopamine depleting agents e.g. methyl-dopa, reserpine. 2. Dopamine receptor antagonists e.g. phenothiazines ( chlorpromazine) & antipsychotic drugs. 3. Estrogen 4. opiates. C) Pathologic causes: 1. CRF. 2. Cirrhosis. 3. Chest wall trauma 6. Pituitary tumours: a) Prolactinoma b) Tumors with pitutary stalk compression 7. Primary hypothyroidism. 1 8. Production from other tumours. Paramalignant 1 1 1 46  Treatment A) Medical ttt ( treatment of choice): 1. Cabergoline: (ergot derivative) - It is a long-acting dopamine receptor agonist with a high affinity for D2 receptors. ! Half-life: range between 63 to 69 hours. ! Side effects: a) nausea & vomiting b) postural hypotension. 11 2.Bromocriptine dopaminergic agonist II ! Aim of ttt: 1) j. hyperprolactinaemia due to any cause. 2) Restores menstruation, fertility 3) stops galactorrhea. 4) Anti-tumour effect t size of the tumour. ! Dose: 2.5 mg t.d.s with meals ( given for 1-2 years). ! Side effects: a) nausea & vomiting b) postural hypote- B) Surgery: Brain 1. Trans-sphenoidal: for micro-adenoma ( < 10 mm ) ! Complications: 1) Hypopituitarism ( 2 ry empty sella synd. ) 2) C.S.F. rhinorrhea. 3) Meningitis. 4) Optic n. damage. 2. Trans-frontal: for large tumours ( > 10 mm ). - In 2rv empty sella: pituitary gland doesn't fill sella completely & surrounded with CSF: ➔ Normal pitutary Function. ➔ Rarely, Hypopituitarism ( from pit. Stalk compression b y CSF) '-- C) Radiotherapy: 4500 rads. 47  VISUAL DISTURBANCES IN PITUITARY TUMORS - Recognizing ophthalmic manifestations of endocrine disorders is critical not only for early & rapid diagnosis and treatment But also to prevent significant morbidity and even mortality. Visual pathway is formed of: 1. Rods & cones: Photoreceptor and start the impulses. 2. Retinal ganglion cells. 3. Optic nerve: Formed by axons of the ganglion cells optic nerve. 4. Optic chiasma: - Site of hemi decussation where the fibers from the nasal part of both retinae pass to the opposite optic tract ➔ - So that the visual information from the right retina passes to the left visual cortex and that from the left retina passes to the right visual cortex. 5. Optic tracts: - Passes from the posterior aspect of the optic chiasma to the lateral geniculate body. - Contains: 1) ipsilateral temporal retinal fibers 2) contralateral nasal retinal fibers. 6. Lateral geniculate body ( L.G.B ): - Site of termination of all afferent fibers of the anterior visual pathway. - Site of the synapse between fibers of the optic tract and that which will form the optic radiation. 7. Optic radiation: Pass from the L.G.B to the visual cortex. 48  8. Visual cortex: - Situated along the superior and inferior lips of the calcarine fissure. - Concerned mainly with macular vision which represented posteriorly and extends variably into the lateral aspect of the cerebral hemisphere, where the peripheral fibers are represented more anteriorly along the medial aspect of the hemisphere. - Area 17: is concerned with perception of form and color. - Area 18 & 19: are concerned with.. a) the recognition of objects b) recalling the visual memory related to objects. Visual Field Defects Visual field deficit ---· ·, --- A) Central scotoma Left eye Retlna---4 B) Monocular vision loss Optic nerve----- C) Bitemporal hemianopia ----+­ E D, G, & H) Contralateral Lateral geniculate homonymous hemianopia nucleus Optic radiations---➔ E & J) Contralateral superior quadrantopia Upper bank of the F & I) Conlralateral calcarlne fissure inferior quadrantopia H (K if the posterior Lower bank of the cerebral artery is occluded) calcarine fissure K) Conlralateral homonymous hemianopia with macular sparing 49  Anatomy of the Pituitary gland ! Chiasmal neural pathways & their relation to pituitary gland: - The optic nerves and chiasma lie above the diaphragma sellae; a visual field defect in a patient with a pituitary tumour therefore indicates suprasellar extension. Ctlt1rr ua.,al Ob res __________ --, -- Ill rd ,·entrlcJe _ Cranio1>h11rynglom11 I LO\\'t'I' nasal fibn> - ___ _ _ ____ 01)t1C cidllSUI ---. -- -'-·'·· -... -~- -. _·. - -- - =" - "· a-c·C- ill"' ----------- Dl1pbra1&ma selh1e --- __ Pos1e1ior clluold AntSO% 5 ml/ kg/ hr). A) Renal causes: 1. Chronic renal failure ( e.g. due to chronic pyelonephritis, chronic glomerulonephritis ) 2. Diuretic stage of acute tubular necrosis. 3. Diuretics in excess. 4. Nephrogenic D.I. 5. Renal tubular acidosis 6. Detoni - fanconi syndrome. 60 B) Endocrinal causes: 1. Diabetes mellitus: ► Specific gravity of urine is high, urine contains sugar ► Blood sugar level is high 2. Diabetes insipidus. 3. Hyperparathyroidism ( calcium diabetes ) & other causes of hypercalcaemia. 4. Thyrotoxicosis. 5. Adrenal causes: a) Cushing's syndrome b) Conn's syndrome c) Addison's disease C) Functional causes: 1. Excessive intake of fluids [ coffee, tea, cola, beer... etc] 2. During winter 3. Hysterical ( lry, psychogenic) polydlpsla: ► Polyuria & polydipsia ► no nocturia. ► Evident emotional disturbances e.g. anorexia nervosa. ► Low urinary osmolality with normal response to dehydration. D) Miscellaneous causes: 1. Multiple myeloma 2. vit. D intoxication. 3. Transient polyuria: may occur after attacks of... ► migraine ► epilepsy ► paroxysmal tachycardia ► bronchial asthma ► intermittent hydronephrosis. Glucose in D.M. l ry pol)1dipsia ◄ j ,vater intake : polyuria.: T solute excretion - Hypotl1alan1ic ◄ ► Nacl in clu·o11ic' pyeloncphritis disease ! tubular rcabsorption & diuretics Drug induced ◄ I polydipsia e.g. atropine ! ADH ( drugs as 11alo.,·o,1e - ce1·1tral D.I. ) Nephrogcnic DJ. 61  -- Treatment - - - ll.a.l!J t!1 Ir,..._..,,:.i a) Hormonal replacement: 1. Aquous vasopressin ( pitressin ) 5-10 units S.C. / 6hrs 2. Desmopressin: 10-20 ug intranasally [ DDVAP, des-amino, d-arginine vasopressin] /12-24 hrs. It has the advantage of not causing: Or ► pallor ► angina ► colic 60-120 mg sublingual Drugs ► bronchospasm ► uterine contraction (Minirin). for central D.I. 3. Vasopressin tannate in oil ( pitressin ) 5 units. I.M./ 48 hrs. b) Non hormonal agents ( 1' ADH ) " in partial DI " 1. Chlorpropamide Tab: 200-500 mg/day. Cap: 500 mg 4 2. Clofibrate times/day 3. Carbamazepine Tab: 400mg/day ! Hydrochlorothiazide or chlorthalidone: Drugs for Diuretics hyponatraemia ! amount of Na 50 mg / day nephrogenic D.I. delivered to the loops of Henle ! water excretion I I; lndome thacin: can be used in ttt of nephrogenic D.I [ 25 -100 mg / d] \ : Other lines of TTT: 1. TTT of the cause. 2. Diet: a) Liberal amounts of fluids are allowed. b) Diet rich in purines should be avoided as it tends to exaggerate polyuria. ®. o&.t 62  Syndrome Of Inappropriate ADH Secretion '' SIADH '' - There is j ADH secretion ( which isn't in response to normal physiologic stimuli ) That t ability to excrete ingested water. ANP -+- Natriuresis -+- Euvolemic hyponatremia Causes 1. Malignancy: e.g. Oat cell carcinoma "of lung". 2. Non malignant pulmonary diseases e.g. pneumonia, T.B. 3. Cerebrovascular accidents. 4. Drugs: e.g. chlorpropamide, cyclophosphamide, vincristine. 5. Miscellaneous: e.g. hypothyroidism, acute psychosis. SIADH Clinically ( water intoxication ) "Soaked Inside" 1. Weight gain. 2. Lethargy. 3. Confusion. 4. Convulsions. 5. Coma. Soaked Inside I Sodium Complications. +osmolality 1. Cerebral oedema 2. Non cardiogenic pulmonary Oedema 3. Central pontine myelinasis [ CPM ] -+- Quadriparesis. DD: other hyponatremic conditions e.g. 1. ATN " non oliguric" 2.CRF 3. Addison's disease 4. OKA 63  Laboratory findings 1. Serum Na< 130 mEq / L ( dilutional hyponatraemia ). 2. t plasma osmolality ( < 270 mosmol / kg). 3. t urine osmolality ( > 100 mosmol / kg) 4. Other investigations: CXR, CT or MRI on the head. -- Treatment 1. Of the cause. 2. Drugs: a) Demethylchlotetracycline ( demeclocycline ). b) Diphenyl hydantoin. c) Naloxone. 3. Restrict water intake. 4. Hypertonic saline infusion ( 5%) in emergency. 5. Diuretics. 6. Aquaretics: vasopressin 2 ( V2 ) receptor antagonists e.g Tolvaptan, Conivaptan. 64  +o w-'11 w-'11 The Thyroid Gland...,.................. 1. Anatomy & Evaluation of thyroid function 2. Thyrotoxicosis 3. Hypothyroidism Causes 4. Adult Hypothyroidism [ myxedema ] 5. Congenital Hypothyroidism 6. Congenital anomalies of thyroid gland..,. 7. Thyroiditis...,.. 8. Goitre...,.. , 9. Tumours of the thyroid 10. Thyroidectomies - 11. Thyroid eye disease ( graves ophthalmopathy).........., 65 -. Scanned with CamScanner -­....... ANATOMY & EVALUATION OF THYROID FUNCTION -.... Anatomy... Internal ------... jugular vein - Superior thyroid artery and vein ---­ Thyroid "r-.JL 1 - Common cartilage carotid artery- ---+-.LtJ'.. Pyramidal Righi lobe lobe lhyroid thyroid ----A Crlcoid Middle thyroid cartilage -­ left lobe Inferior.... thyroid thyroid artery--- r--::==-='-.1...,'!'t\ Isthmus.... Pre tracheal ,_ of thyroid lymph node _.J::::::::5_.. _. Inferior thyroid vein----/ _. HyoidBone.... 2 Lobes - Isthmus Levator glandutae thyroidae _.. -@( }i-i=1k'ml,Ji La geal Pyramidal lobe _.. Prominence Rt. Lobe._.- Crlcothyrold ligament ---► Lt. lobe mus Relations - ------- Thyroid gl.-:ind f'\wmfdollotic Left------:: ------ Trachea thyroid lobe Esophagus----,,.-:;,..:;.-.,.--...,...; ,---- Right lhyroid Internal ----,1"""'- lobe 1ugular vein.---- Parathyroid Cornmon---J:+---r- carotid ar1ery Vagus nerve -tft,t--:55 Scanned with CamScanner  Histology Physiological effects of thyroid hormones 1) l 02 consumption in all tissue - glucose absorption. 2) l HR, Cop, excitability & conductivity (+arteriolar dilatation ). 3) T skeletal growth & sexual maturation. 4) ! serum cholesterol level. Thyroid hormone synthesis A) Iodine trapping: - Iodide absorbed from the intestine circulates in the blood & is picked up by the thyroid under the effect of TSH where it is converted to iodine ( by the peroxidase enzyme ). B) Binding: iodine+ tyrosine lodlnase cni ► Mono-iodot¥(osine or Oi-iodotyrosine. C) Coupling: Mono-iodotyrosine + Di-iodotyrosine -+ tri-iodothyronine ( T3 ) Dt-iodotyrosine + Di-lodotyrosine -+ T4 ( thyroxine ) D) Releasing: T4 & T3 combine with globulin to form thyroglobulin prote35 c ► T4, T3. - Release of thyroid hormones is controlled by TSH which depends on the feed back mechanism. - Thyroid hormones in the circulation are bound to plasma proteins: ;. mainly thyroxine binding globulin ( T.B.G ) 75%, ► prealbumin 15%, ;. albumin 10%. 67 ------------ -- ijM Scanned with CamScanner..... LUMEN (COLLOID) (b) Oxldado (b) lodlnati n (Mm (b) Coupling (8... 1 r,r. Apical r TPO+H202 Tg TPO+H 1 Tg... membrane.. THYROCYTE Colloid resorption (c) \... (d)+ Tg proteolysis (d)... ◄ (e) Delodination _ ____.i.::.L-=-..:.:......,;______ , MIT DI T... Basolatcral membrane T1-1 T. ► T,... (f) (a.... INTERSTITIUM r ------------ -- -Hormone secretion... Hypothalamus...... TRH Other tissues... ', Anterior... pituitary... TSH '.... ' '.... I I_.. T4 and T3. T4 and T3 + TBG ► TBG·T4... TBG·T3... Evaluation of thyroid function... 1. Measurement of free T3, T4: ( 0.4 ng / di, 1.6 ng / di respectively )..... _. 2. Measurement of total T3, T4: [ By RIA]... a) Total T4 ( normal: 4-12 ug / di ) b) Total T3 ( normal: 80 - 120 ng / di )..,;,.... 3. Hormones which control the thyroid:.... a) Serum TSH: ( normal: 0.27 - 4.5 uU / ml)...... - It is the most sensitive test for lry hypothyroidism. Thus, it can differentiate between lry ( j ) & 2ry hypothyroidism ( ! ). - In hyperthyroidism: low in primary hyperthyroidism ® 68... Scanned with CamScanner  b) TRH stimulation test: - Normal response -+ a rise of TSH.... - l or absent response -+ a. Hyperthyroidism b. Secondary (pituitary) hypothyroidism -- - j response --+ lry hypothyroidism. --.. c) T3 suppression test: -­ - Serum T4 or RAIU is compared before & after T3 administration --+ a failure of.... suppression is diagnostic of hyperthyroidism. N.B; Total T3. T4 are affected by changes in TBG.. -­ 1. Pregnancy. 1. L.C.F... 1. Oestrogen. 2. Nephrotic syndrome... 2. Congenital. 3. Malnutrition... 4. Congenital. 5. Androgens. -- I.. 4. T3 resin uptake: (normal= 25-35%).. Labelled T3 + patient's serum + resin ( bind the free hormone ):...... a) In thyrotoxicosis --+ T3 resin uptake j ( T3 RU j ) [ binding sites of TBP are nearly saturated with thyroxine ].... b) In hypothyroidism --+ T3 resin uptake! (T3 RU J )... 5. Free thyroxin index ( FT4 I):.. FT41 = T4 (total ) X T3 resin uptake T3 RU "111.easu1·ed".... Mean 11.ormal T3 RU - Normally: 4.5-11. 5 ! T total T4 & j T3 RU.... - Not affected by changes in TBP: e.g. ! TBP -+.. - It is sensitive test when abnormality in TBP is suspected. - Now, it is replaced by measurement of free T3 & T4. , _____________________ 69 __::.... Scanned with CamScanner ,-) 6. Radio-active iodine uptake: c 11 11 or 1 121 " preferable") R.A.1.U ,-t - Normal uptake ( 24 hours after giving the isotope ) ➔ 5-30% of the adminstered dose. - Useful in the diagnosis of hyperthyroidism.... ,..... R.A.1.U. is less useful in diagnosis of hypothyroidism because it discriminates poorly.... between low & normal uptake....... ! Most causes of thyrotoxicosis lead to j R.A.I.U. except:.... 1) Thyrotoxicosis factltia ( due to thyroid hormone intake), 2) Jod Basedow phenomenon. Ill-)..... 3) Thyroiditis ( subacute & chronic ). 4) Ectopic thyroid tissue e.g. struma ovarii & functioning metastatic thyroid carcinoma 1.-t........ 7. Antithyroid antibodies: 1) Thyroid stimulating immunoglobulin "TSI ": previously called... long acting thyroid stimulator LATS) or TRAb" thyrotropin receptor antibody" In Graves' disease. 2) Antimlcrosom al & antithyroglobulin antibodies: in Hashimoto's thyroiditis. 3) TSH binding inhibitory immunoglobulin ( TBII ): In lry hypothyroidism. 4) Serum thyroglobulin: j in differentiated cancer thyroid. 8. Thyroid scanning ( using 99M1c ) of value for: 1. Define areas of T ( hot nodule ) or !, ( cold nodule) uptake. 2. Retrosternal goiter. 3. Ectopic thyroid tissue. 4. Functioning metastasis of thyroid carcinoma. 9. Other tests: 1) Ultrasonic exam ination ( ± FNAB ) of the thyroid for: 1. Differentiation of cystic from solid nodules. 2. Assessment of changes of the size of thyroid nodules in response to ttt. ® 70 Scanned with CamScanner --------------- -· 2) Basal metabolic rat 50 yr - Toxic MNG" multi nodular goiter": plummer disease. - Antithyroid antibodies can help in the differentiation ® _____________________________ 78 _) Scanned with CamScanner  Treatment 1. Medical: 1) Thyrotoxicosis In pregnant @ 1) Huge goiter-. pressure symptoms 2) Cases complicated by H.F. 2) Retro sternal 3) Graves' disease in a patient< 25 years 3) Suspicion of malignancy. 4) Pre-medication before operation. A) Thionamide drugs:.Z Mechanism of action: 1) Inhibit thyroid peroxidase: ! synthesis of thyroid hormones. 2) Propyl thiouracil: ! peripheral production of T3 from T4. 3) Carbimazol: ! production of TSI ( LATS) " immnuo-suppressive effect 11 :- Dose: 1) Propyl thiouracil: 300 - 600 mg/ day ( in 3 divided doses). 2) Methimazol: 30 - 60 mg/ day ( once daily or in 3 divided doses) 3) Carbimazol ( Neomercazol ): 30 - 60 mg/ day ( once daily or in 3 divided doses)....: Follow up:... - The dose can be decreased to 1/2 - 2/3 the initial dose ( after control 4-6 ws of the.. disease)... - Therapy should be maintained for 1-2 years to induce long term remission..,... : Side effects:... 1) Agranulocytosis ( do blood examination on feeling sore throat)... 2) Arthralgia... 3) Skin rash. 4) Serum sickness... 79 Scanned with CamScanner  : Prognosis: 1) Long-term remission "when course is completed" in 1 /2 pts. 2) Relapses usually occur within the 1 st year after stopping therapy. 3) Some pts develop hypothyroidism after a long time after ttt. B) Beta adrenergic blockers: Propranolol ( inderal) is used. : Mechanism of action: a) t excessive adrenergic activity. b) ! conversion of T4 to T3 : Dose: 20 - 40 mg / 6 hrs ( adjusted to ! H.R. to about 80 / m ). C) Other agents: 1. Na ipodate ( orographin): 1 gm / day--+ ! T4 to T3. 2. K iodine " Lugol's iodine 11 ► mainly used to prepare patient for surgery ( by! gland vascularity). ► 5 drops ( 250 mg) bid But escape from its effect occur after 10 days. 3. Dexamathazone ► 8 mg/day. Wolff chaikoff effect ► ! secretion of thyroid hormone Short period of thyroid H. suppression, ► ! T4-+ T3. with large amount of iodine ingestion. ( e.g. amiodarone) 2. Radio - iodine 131 therapy: 1) Recurrence after thyroidectomy. 1) During pregnancy, lactation & childhood 2) After failure of medical ttt & 2) Huge & retrosternal goitre. the patient is unfit for surgery. 3) Patients In whom surgery is indicated but refusing the operation. 80 Scanned with CamScanner -.... Dose: 4 - 10 mlllicuries. ( Side effects:: 1) Hypothyroidism: ,. If it occurs within the 1'1 6 ms after ttt - transient. ,. If occurs after one year -+ permanent. 2) May cause thyroid carcinoma ( recently, No l incidence of malignancies}. 3) Foetal abnormalities & hypothyroidism of the new born if given by mistake during pregnancy... - May be used in childbearing age but avoid pregnancy 6ms after the dose - Some patients may show acute release of the hormone on initiation of the ttt... So, thionamlde drugs have to be gtven before 1 131 & stopped 3-5 days before -­ giving 1 131 nin order not to Interfere with the uptake of iodine".... to be restarted 14 days later -­ - Antithyroid drugs may be given for next few months since radio-iodine doesn't... achieve its effect till then.. [ euthyroid state is gradually restored over aperoid of 6 ms]...... 3. Surgical management:....... : Indications:.. 1) Nodular toxic goiter & solitary toxic nodule. 2) Failure of medical treatment or recurrence after successful ttt... 3) Huge diffuse toxic goiter with pressure symptoms... 4} Retrosternal & intra thoracic toxic goiter... 5) Suspicion of malignancy...... ______________________________ M.___ _ 81 Scanned with CamScanner  ! Preoperative preparations:.. 1) Preoperative investigations as before.... 2) Sedatives.... 3) Antithyroid drugs ( unless contraindicated e.g. retrosternal goiter}. 4) lnderal that is continued for 1 week after operation. 5) Lugol's Iodine 2 weeks before operation ( not more) together with ATDs. 111111.. Some surgeons advocate to replace the antithyroid drugs 15 days before the ,... operation with Lugol's Iodine ➔ To reduce the size and vascularity of the gland, others omitted Lugol's Iodine..... ! Operation: Subtotal thyroidectomy........ - where we leave part of the gland that is sufficient to maintain the patient euthyroid........ - This is estimated to be 1/3 of a normal thyroid lobe on each side about:.... 1) 5 - 10 gm of the gland or 2) 1/8 of the goitrous gland. -,.... Thyroidectomy.... ! Steps & technique & complications: see later........ 4. Treatment of pregnant Cf).... 1) l131 : is contra-indicated because it can cross the placenta. _.. 2) Propyl thiouracil: crosses the placenta to lesser extent than the other thionamide.... preparations, so it Is the preferable drug..... 3) Surgical thyroidectomy: [ If necessary]➔ best performed In the 1st or 2 nd trimester because general anesthesia in the 3 rd trimester may lead to premature labour. _.....-) - The newborn: may develop hyperthyroidism due to transplacental transmission of TSI.... so, special attention must be paid for him. Carbimazol: can cause aplasia cutis in the newborn if used in the 1 st trimester but no harmful effect after 1 st trimester. 82 Scanned with CamScanner  --- - 5. Treatment of thyrotoxic crisis:.--...,...... 1) Ice bags ( to control hyperpyrexia).... 2) fluids & electrolytes. 3) I.V. Dexamethasone: 4-8 mg/ day (unless contraindication by severe infection). r-'11 4) I.V. propranolol: 1mg/ 5 min. up to 10 mg to i H.R. e-11 S) lpodate ( Na ipodate ): 1 gm/ day for 2 weeks. 6) Antithyroid: in a large dose -. propyl thiouracil ( 6 00 mg then 300 mg/ 6h. ).... e-tl 7) Antibiotics: to control an underlying infection. 8) K - iodide. 6. Treatment of complications: 1) Pretibial myxeodeam: alocal steroids. 2) AF: control thyroid state, If persist -. D.C. " avoid amiodarone " 3) Protection of eyes: Guanithldine eye drops. lateral tarsorrhaphy. 4) For exophthalmos: prednisone or decompression operation................ ,.... 1-4.... 1-11 83 cW[h... ,lii',I Scanned with CamScanner ,.a... HYPOTHYROIDISM CAUSES........ A) 1 ry hypothyroidism (95 °/o):...... ! Causes:..... _.. 1) Congenital developmental defect 1) Pendred syndrome: ,... Inherited biosynthetic defect 2) Post surgery. {+congenital deafness )...... 3) Post 1 131 therapy, external neck 2) Iodine deficiency _. endemic goiter.... irradiation. 3) Maternally transmitted: 4) Idiopathic: Myxoedema " 11 a. anti thyroid drug or It may be associated with.... b. !131 during pregnancy 114 1. Antithyroid antibodies or 4) Drug induced:... 2. antibodies to TSH receptors. a. Amiodarone b. interferon... 3. auto- antibodies to other c. lithium. d. Antithyroid drugs endocrinal glands. 5) Chronic thyrolditis: Hashimoto's disease 4. other auto-immune disease e.g. _.. 6) Self limited: ► SLE, _.. ► myasthenia gravis. a. Subacute thyroiditis..... b. Post partum thyroiditis autoimmune" II _.. 7) Infiltration: by tumour. _. _.... B) 2ry hypothyroidism ( 5°/o ): Due to hypothalamic or pituitary disease C) Tissue resistance to thyroid Hormone ( rare ) 84 Scanned with CamScanner  ADULT HYPOTHYROIDISM [ MYXEDEMA] - It is much common in @ than (!} ( usually between 30 - SO years ), mostly auto- immune process ( circulating thyroid antibodies in > 80% of cases ). Clinical picture 1. Neurological manifestations: 1) Reduced memory, mental slowing, dementia may occur" Myxedema madness ".... 2) depression. 3) Delayed relaxation of tendon jerks ( suspended jerks )... 4) Mucinous infiltration:.. In the flexor retinaculum --+ carpal tunnel syndrome.... In the vocal cords --+ hoarseness of voice. In the internal ear --+ progressive deafness... In the tongue -+ slurred speech. -­ Myotonia, muscular hypertrophy" Hoffman syndrome 11, proximal myopathy.. PN & thickening of nerves.... 2. Cardiovascular + haematological manifestations:.. 1) Sinus bradycardla.... 2) Cardiomyopathy --+ heart failure... 3) Cholesterol pericarditis & pericardia! effusion... 4) Atherosclerosis --+ angina pectoris & intermittent claudication... 5) Hypertension due to T peripheral resistance... 6) Anaemia:.. ► Normocytic: due to bone marrow depression & i peripheral 02 requirements... ► Megaloblastic: due to associated pernicious anaemia... :.- Microcytic hypochromic: due to menorrhgia & achlorhydria... 85.. - Scanned with CamScanner  3. GIT manifestations: 1) Adynamic ileus: ;.. Constipation. , Intestinal obstruction. 2) Achlorhydria ( often associated with pernicious anaemia ). 3) Ascitis ( with high cholesterol content ). I 4. Musculoskeletal manifestations: Arthralgia & joint effusion & stiff muscles r-t... 5. Skin & hair manifestations: Puffy face & coarse features.... t.t:> Pathogenesis: Accumulation of glycosaminoglycans mainly hyaluronic acid in skin &... S.C. tissue retaining Na & water.... a. Skin: -­ _, 1) Ory cold skin. 2) Orange due to accumulation of carotene ( carotene thyroxine► Vit. A) 1-=f 3) Malar flush. I_.... _. b. Hair: _, 1) Sparse, brittle, coarse..... 2) Loss of hair from the outer 1/3 of the eye brows and eye lashes ( madarosis )..... c. Xanthelasma: due to j cholesterol......... -, _.............. --- --- "'· I _, 86 Scanned with CamScanner -.. -- -- 6. Reproductive manifestations: 1) Menorrhagia II due to anovulatory cycles 11 -4 The commonest...... 2) Amenorrhea & galactorrhea In cases associated with hyperprolactinaemia (late). 7. Renal manifestations:... 1) ! excretion of a water load hyponatraemia ( may be due to SIADH )...... -4 8. Pulmonary manifestations:... 1} Pleural effusion... 2) ! ventilatory response to hypoxia & hypercapnia CO2 retention.... 3} Sleep apnea syndrome....... 9. Metabolic & endocrinal manifestations:.... 1) Growth & development retardation in children ( Juvenil myxoedema)... 2) Growth hormone deficiency ( because thyroxine is necessary for GH synthesis}... 3) Gain of weight ( despite ! appetite)....... 4) Hypothermia & cold intolerance... 5) Hyperlipidaemia ( due to ! lipoprotein degradation). 10. Thyroid gland: may be...... 1) Atrophic... 2) Enlarged ( in goitrous hypothyroidism)... 3) Show evidence of previous thyroldectomy..... 11. Myxoedema coma: : Causes:....... 1) Old standing, untreated hypothyroidism. 2) Hypothyroidism with exposure to: ;. Coldness ► Infection ► Trauma ► CNS depressants. 87 Scanned with CamScanner...a ! Clinical picture:... - 1) Subnormal temperature. 2) External features of severe hypothyroidism & bradycardia. __.. - 3) Dllutional hyponatraemia. 4) Alveolar hypoventilation -. CO2 retention & narcosis.... Investigations........ 1. See evaluation of thyroid function..... _.. Subclinical hypothyroidism:- j TSH & low normal T4, T3...... 2. X-ray chest & heart: pericardia! effusion or pleural effusion..... 3. ECG: low voltage, bradycardia.... Differential diagnosis -t 1. 1 ry & 2ry hypothyroidism: (see before)... Also in lry --+ Non Goitrous & Goitrous -ii _. 2. Sick euthyroid synd." low T3 syndrome": _..... - Thyroid dysfunction in non thyroidal illness.... 3. Nephrotic syndrome 4. Chronic renal failure... 1) Facial puffiness & pallor. 1) Facial puffiness & pallor.... Similar to... 2) Hypercholesterolaemia. 2) Hypertension. myxoedema _.. in: 3) l Total T4, T3 3) Dry skin..... ( due to loss of T BG in urine}..... Different 1) Normal TSH. 2) Heavy proteinuria. 1) Polyuria. 2) pruritis. -9 from... myxoedema 3) Normal thyroid function. _, In: 4) impaired kid. Functions...., 88... Scanned with CamScanner  Treatment 1. Preparation: 1) Na Levo-thyroxine ( L-thyroxine) -+ of choice. 2) Dessicated thyroid extract: ( T4 : T3 - 4 : 1 ] 3) Synthetic T3: there is no real indication for its use because T4 is converted to T3 in the body) 2. Rapid correction in: 1) Neonatal, infantile & Juvenil hypothyroidism. 2) Myxoedema coma. 3) Hypothyroid patient prepared to emergency surgery: I.V. adminstration of L-thyroxine + hydrocortisone is indicated. 3. Slow correction:..... - In elderly patients or patients with heart disease start with 25 - 50 ug / day, j the dose by 25-50 ug every month ( according to the clinical response)..... until reaching 150 - 200 ug ( full replacement dose)...... 4. Clinical response: Full effect is likely to take 2-3 months................ 5. Monitoring the replacement dose: T4: becomes normal within few days,..... T3: ( better) in 2 - 4 weeks...... TSH: in 6-8 weeks...... ! 1 I r of myxoedema coma:..... I.......... 1. l-thyroxine: 500 ug i.v. 2. Hydrocortisone: 100 mg ( for possible associated adrenal insufficiency )....... 3. Hypertonic saline (+glucose)....... 4. Assisted ventilation. 5. Avoid further heat loss. 89 '------------------------------ Scanned with CamScanner ,..,... &ONGENITAL HYPOTHYR81DISM... - Congenital hypothyroidism is one of the most common preventable causes of intellectual disability.... Incidence....... - Occurs in approximately 1 in 2,000 - 4,000 live births. - Female: Male ➔ 2: 1. Causes....... A) Thyroid defect ( Primary hypothyroidism) { L T3, T4 ): 1. Thyroid dysgenesis: ( most common about 85%) 1) Aplasla,... 2) hypoplasla,.... 3) ectopic gland ( lingual, sublingual or sub-hyoid). """... 2. Dyshormonogenesis ( 2nd common 10%): AR + goiter + its types are:.... 1) Iodide transport defect. __.. 2) Organification defect: due to lack of thyroid peroxidase enzyme...... 3) Thyroglobulin synthesis defect.... 4) lodotyrosine deiodinatlon defect..-..... 3. Transient hypothyroidism:..., - Due to transplacental passage of maternal antithyroid drugs or antibodies to TSH -' receptors..... - Neonatal exposure to excessive iodine containing antiseptics...,..., 4. Maternal iodine deficiency: due to Iodine deficiency.... 5. End organ resistance to: TSH or T3 or T4 ( pseudo - hypothyroidism)., 90... Scanned with CamScanner B) Pituitary defect (Secondary hypothyroidism) ( ! TSH ): 1. Isolated 2. With multiple pituitary deficiencies. C) Hypothalamic defect ( Tertiary hypothyroidism ) ( ! TRH ) Clinical manifestations of congenital hypothyroidism a) At birth: usually are subtle. b) In the newborn: 1. Hypothermia 2. large fontanels 3. Prolonged jaundice I 4. Mottled skin. 5. Acrocyanosis 6. Abdominal distention 7. Edema 8. Constipation 9. Respiratory distress 10. Lethargy & poor feeding 11. Umbilical hernia 12. Large tongue 13. Dry skin 14. Hoarse cry. c) Full clinical picture of hypothyroidism: 1) Growth retardation ➔ proportionate short stature. 2) Delayed cognitive development ➔ mental deficiency 3) Delayed motor milestones. 1. Muscle weakness 2. Hypotonia 3. constipation 4. potbelly 5. Myxedema coma ( carbon dioxide narcosis, hypothermia ) 6. Pseudohypertrophy of muscles 7. Myalgia 4) Neuromuscular 8. Physical and mental lethargy 9. Developmental delay 10. Delayed relaxation of reflexes 11. Paresthesias 12. Cerebellar ataxia 13. Umbilical hernia 91 Scanned with CamScanner  1 Myxedema... 2 Serous effusions ( pleural, pericardia!, ascites )....... 3. Hoarse voice (cry) 4 Weight gain.... 5) metabolic 5. Menstrual irregularity 6. Arthralgia..... 7. Elevated CK 8 Macrocytosis (anemia) _. 9. Hypercho I esterolemia 11. Precocious puberty in severe cases 10. Hyperprolactinemia _.. 1. Poor growth 2. Dull facies: thick lips, large tongue, __. 3. depressed nasal bridge 4. Periorbital edema ,.. 6) Ectodennal 5. Ory scaly skin 6. Diminished sweating 7. Sparse brittle hair 8. Vitiligo _.. 9. Carotenemia...... 1. Sinus bradycardia 2. Heart block 3. Cold extremities.... 7) Circulatory 4. Cold intolerance 5. Pallor.... 6. ECG changes: low-voltage QRS complex _. 1. Delayed bone age.... 8) Skeletal 2. Epiphyseal dysgenesis, 3. increased upper- to- lower segment ratio -.I............... -"............,...,..., __, 92 Scanned with CamScanner  -­... Diagnosis of hypothyroidism.. A) Newborn screening test:...I w-1.. - Is crucial to make an early diagnosis and initiate treatment before 1 month of age..... B) Thyroid function tests: 1. Low serum T4: ( normal level= 4 - 9 ug / di ) 2. Low free T4.. In hypothyroidism: there's compensatory increase in peripheral conversion of.. T4 to T3; so measuring of T3 may be misleading...... 2. Serum TSH: ( normal level< 7 IU / ml post neonatal ).. The most sensitive screening test for primary hypothyroidism High in primary hypothyroidism ( > 20 IU / ml).. Low in secondary & tertiary hypothyroidism... In pseudo hypothyroidism -+ all [ T4 & T3 & TSH ] are high....... 3. High serum cholesterol & anemia... ljiI l l,;j Normal TSH.... 1l1J... LowT4... Primary hypothyroidism LowT4.... 1. Secondary hypothyroidism [ pituitary or hypothalamus ]...... Normal T4 2. Severe nonthyroidal illness.. Subclinical hypothyroidism... 93....- Scanned with CamScanner ,-)... C) Radiological:....... 1. Delayed bone age: - At birth: absent distal femoral epiphysls I by knee x-ray)....... - Later on: delayed appearance of ossific centers ( by wrist x-ray)... - Eplphyseal dysgenesis: multiple foci of ossification in heads of femur & humerus..... 2. Skull x ray: intra-sutural ( Wormian) bones, large fontanels.... __.. 3. Chest x ray: may show cardiomegaly. Cretlnold 4. CT & MRI: for pituitary tumours. eplphyseal... dysgenesls... D) ECG: Slow and low voltage Shortening of.... long bones _.. E) Echocardiography: cardiomegaly..... ,.... F) Investigations to detect the cause:..... 1. Thyroid scintigraphy ( using radioactive 1 123 )..... Absent uptake in aplasia or iodide trapping defect _.. Increased uptake in dyshormonogenesis..... Localize ectopic thyroid......... 2. TRH stimulation test: done only with ,J, TSH... ,,,,,4 3. Differentiate between hypothalamic & pituitary defects: _..... by I.V. bolus of TRH:.... If T4 increases -+ hypothalamic defect ( tertiary hypothyr.). If T4 does not increase -+ pituitary defect ( 2ry hypothyr.). 94 Scanned with CamScanner  Treatment ! Replacement therapy of L-thyroxine ( L - T4 ): - Early treatment within the first month ➔ excellent prognosis. - If delayed after 6 months ➔ the intellectual function is markedly decreased. : Dose: ► O to 3 months: 10 - 15 mcg/ kg/ d ► 3 to 12 months: 6-10 mcg/ kg/ d ► 1 to 3 years: 4 - 6 mcg/ kg/ d ► 3 to 10 years: 3 - 5 mcg/ kg/ d - l-T4 tablets crushed and mixed with a 1 to 2 ml of water or breast milk administered... orally at the same time each day.... - Dose is adjusted according to clinical response:-... Overdose: diarrhea, fever, tachycardia, increased appetite... Low dose: constipation hypothermia, bradycardia, decreased appetite.... ! Follow up:... a} Clinical: monitor activity, milestones, and growth... b} Laboratory: monitor T4 & TSH levels.... c) Radiologic: monitor bone age & ossific centers........ ,,.. A) Before treatment: B) After treatment:.. - puffed eye , ,... - alert looking...... - dull looking face - swelling less.. - protruded tongue - tongue inside... A ____.._.____._ ,---- 1..:B=----------'... 95 L---------------------=----' ® M r.- fl!" Scanned with CamScanner.. CONGENITAL ANOMALIES OF THYROID GLAND......... 1. Thyroglossal cyst............ _...... ·.--........ Thyroglossal cyst... -­ Etiology: It is due to persistent unobliterated portion of the thyroglossal duct _.. ( tubulo-dermoid ) "'4... Pathology.... _.. ! Site: - Any site in the course of thyroglossal tract from fora men caecum to the thyroid ismuth....... - But the commonest site: is below the hyoid bone ( infrahyoid ). : Structure:....... - A thin wall cyst lined with stratified columnar, cubical, or squamous epithelium.... - It may contain islets of thyroid tissue and may be connected to lymphatics of the neck.... which make it liable to infection. - It contains clear viscid or mucold fluid. - It is connected with a thin fibrous band to the hyoid bone...., 96 Scanned with CamScanner  Complications: Infection abscess which drains spontaneously or surgically fistula Incidence: It may be dated since birth but commonly, It appears in childhood. Clinical picture 1) A tense cystic swelling in the midllne of the neck or slightly to the left usually just below the hyoid bone. 2) It moves up & down with deglutition and moves upward with protrusion of the tongue 1) The fibrous track connecting it to the hyoid may be palpable. Investigations: Neck U/5 to ensure the diagnosis. Differential diagnosis: From other swellings in the midline of the neck. Treatment: Sistrunk operation - Complete excision of the cyst with its track up to the foramen caecum of the tongue. - To ensure complete excision, the central part of the hyoid Is resected, multiple transverse incisions ( ladder step incision } may be required. 97 Scanned with CamScanner ,.,.... Thyroglossal Fistula.... Etiology Always acquired....... 1) It follows spontaneous or surgical drainage of an infected thyroglossa... 2) It may follow incomplete excision of the cyst with its track....... Clinical picture...,.., 1) There is a history of an abscess that was drained spontaneously or surgically.., 2) Followed by a persistent small opening that continues to discharge serous or... seropurulent discharge..... 3) Characteristically, the opening moves up with protrusion of the tongue with formation.., of cresentic skin fold above. _,