THYROID DISORDERS

Thyroid disorders are very common, even more so in females. Physiology of thyroid harmones: Thyroid gland secretes mainly T4, by iodination.T3, which is active harmone is mainly formed by peripheral conversion of T4.(as shown in the diagram) Majority of T4 formed is bound to proteins li e thyroid binding globulin (T!"). #o, free T4 is better indicator of thyroid diseases, rather then total T4 as many conditions can increase T!" (li e pregnancy, $% pills) or decrease the levels of T!" (steroids, nephrotic syndrome). &evels of T3, T4 and T#' and T(' are controlled by negative feed bac phenomenon. (as shown in the diagram). $ther investigations done thyroid diseases) 1. Thyroid upta e s!an: *sing +,-3, + ,3,, Tc .., can assess thyroid gland function. +ncreased upta e is seen in grave/s disease, to0ic nodular goiter. 1ecreased upta e is seen in thyroiditis, antithyroid drugs.

-. Thyroid anti"odies: Thyroid receptor antibodies are seen in grave/s disease. 2ntibodies to thyroglobulin and thyropero0idase are seen in hasimoto/s thyroiditis. #. $ltra sound of thyroid and %&'(: *ltra sound of thyroid mainly done to identify nodules and 342% can be done from these nodules.

HYPOTHYROIDIS)
(lini!al features: %linical features and causes are given the bo0. 5rolong hypothyroidism causes infiltration of mucopolysaccharides and hyluronic acid deposition in various tissues causing large tongue, non6pitting edema etc. In*estigations: %lassical findings of primary hypothyroidism are reduced levels of T3 and T4 and increased levels of T#'. #econdary hypothyroidism T3, T4, T#' all are reduced, along with other pituitary harmones. $ther abnormal investigations are 2nemia 7macrocytic or microcytic (mennoraghia). 8%"66 bradycardia, low voltage comple0es. +ncrease in &1', %9, and 2#T. 'ypercholesterolemia. 2ntibodies to thyroid pero0idase are positive in spontaneous atrophic thyroiditis and hashimoto/s thyroiditis. Thyroid scan shows reduced upta e. Treatment: (eplacement with thyro0ine (T4) or T3 is the principle management of any hypothyroidism. Treatment is for life. *sual staring dose is :;6,;;micro gms per day. Then gradually increase the dose based on T#' and symptoms. (epeat T#' once in < wee s to -months.

 +n6patients who have ischaemic heart disease and elderly patient/s starting dose should be less (,-.:6-:micrograms=day). 1ose of thyro0ine may go up during pregnancy.

S$+(,I&I(', HYPOTHYROIDIS)
This term is used when T#' is elevated and T3, T4 are normal with vague symptoms. This condition should be treated only if the 'igh titers of antibodies &ipid abnormalities 2ssociated with goiter +f above indications are not present then patient should be followed up with T#' andT3, T4 every 36< months.

)Y-EDE)' (O)'
My0edema coma is medical emergency. %ommonly seen in elderly patients with longstanding hypothyroidism. %ommon precipitating factors are infection, trauma, ".+ bleed, and stro e etc. Mortality is :;>. %linical features) 2ltered sensorium(including coma and sei?ure) 'ypothermia !radycardia and hypoventilation 'ypoglycemia and #+21'. 2lways send for serum cortisol along with thyroid harmones to rule out 2ddison/s crisis. Management should be started with out waiting for the reports.

 +.@ thyro0ine (T4) :;;micro gms stat and ABhly. +@ triidothyro0ine can also be given. +n +41+2 +.@ preparations are not available so oral thyro0ine is used. +ng. 'ydrocortisone ,;;mg +.@ ABhrly should be given and can be stopped if cortisol levels are normal. $ther measures include) $0ygen and gradual rewarming. "lucose and sodium correction. @entilatory support if reCuired.

H'SI)OTO.S THYROIDITIS
+t is autoimmune thyroiditis. %ommon in middle aged females. "land is diffusely enlarged and is firm. 5atient may be euthyroid or hypothyroid. 2ntiT5$ 2b is positive. Treatment is reCuired only if there is hypothyroidism or goiter.

HYPERTHYROIDIS)
(lini!al features: "rave/s disease is commonly seen in females of age group of -;64;yrs. +t is auto immune disease, due to +g" antibodies that stimulate T#' receptor +t is commonly associated with autoimmune disorders li e pernicious anemia, myasthenia gravis. $pthalmopathy is very common but dermopathy is rare. Majority of the patients has fluctuating, relapsing and remission course. Thyroid acropachyDclubbing and swollen fingers, this very rare. 5atients may develop pretibal my0oedema. Diffen!ial diagnosis: 2n0iety states (etroorbital tumors '+@ disease. In*estigations:

 Typical finding are increased T3 and T4 and mar edly reduced T#'. $ccasionally only T3 may be raised with suppressed T#' ( T3 to0icosis) Thyroid scan "rave/s diseaseDdiffusely increased upta e. To0ic nodular goiterDincreased nodular upta e and suppressed upta e in other areas T#' receptor antibodies are positive. Mild elevations of bilirubin, 2#T,""T may be seen +ncreased in 2&5 may be due to increased bone turn over. Mild elevation can also seen in calcium and glucose. Treatment: There are 3 treatment options for patients of hyperthyroidism ,) 2ntithyroid drugs -) (adioactive + ,3, 3) #urgery 1/ '&TITHYROID DR$0S1'TD/: +ndications for 2T1 areDall patients 2T1 are initial treatment of choice, they are also given even before surgery and radioactive + ,3,. 1etails of the drugs are given in the bo0. %linical benefit is seen only after ,;6-; days. !etabo ers are only for rate control and for tremors.

 1rugs should be started on high dose and slowly taper every 46< wee s based no clinical and thyroid profile. They should be tapered to lowest dose once patient is euthyroid and continued for ,B months in case graves disease. 2+lo! and Repla!e3 regimen 666 full dose of anti thyroid drugs and ,;; micro grams of thyro0ine for ,B months. Indi!ations for surgery4 Radioa!ti*e I 1#1 2ge of the patient E 4; or F 4; yrs. 1rug side effects and compliance 3itness for surgery. 5atient/s choice -) R'DIO'(TI5E I 1#1 Treatment of choice for the patients older than 4; yrs. + ,3, is contraindicated in pregnancy and lactation. 5atients should be made euthyroid with anti thyroid drugs and stopped 364 days before the procedure. %omplications) 4ec discomfort Gorsening of hyperthyroidism 'ypothyroidism esp. after ,;6,: yrs. 6/ S$R0ERY:

 #urgery is indicated for patients below 4;yrs and who have not completed her family. 5atient is made euthyroid before surgery with antithyroid drugs and then stopped ,;6,4 days before then start 9+ drops, to reduce vasularity of thyroid gland and minimi?e post operation complications. (ompli!ations: ,) Tracheal compression(post op. bleeding) -) &aryngeal nerve palsy. 3) 'ypocalcemia (parathyroid resection) 4) 'ypothyroidism :) Thyroid storm. )anagement of opthalmopathy: Methycellulose eye drops and tinted glasses for dry eyes. #ystemic steroids if there is reduced visual acuity. 8ye muscle surgery for diplopia. Tarsoraphy for corneal surgery.

Management of dermopathy is rarely reCuired, if it is severe then local steroids can be used. Thyroid !risis4storm (are but life threating clinical emergency. %ommon precipitating causes are) ,) +nfection. -) *nder prepared surgery.

2fter + ,3, treatment. (lini!al features: %ommon in elderly patients 3ever and agitation Tachycardia %%3 +nvestigations show T3 and T4 high and T#' suppressed. Treatment: ,) %arbima?ole ,:mg CBhry (to suppress synthesis of thyroid harmone). -) &ugol/s +odine or radiographic contrast medium (to suppress the release of thyroid harmones. 3) +.@ or oral propranalol B;mg C<hly (to inhibit the systemic effects of thyroid harmones. 4) This treatment is continued until patient becomes euthyroid both clinically and biochemicaly then continue carbima?ole.
3)

Hyperthyroidism in pregnancy should be treated with antithyroid drugs. Both the drugs are safe but should be given at lower doses. If there is no response then surgery should b considered. I 131 is contraindicated in pregnancy

0OITRE
"oitre means thyroid enlargement. #imple goitre can be diffuse, multinodular and to0ic multinodular. @arious causes of goitre are given in the bo0. (lini!al features: 2symtomatic 7very common 3eatures of hyper and hypothyroidism. 5ressure symptoms can be there in the form of dysphagia (esophagus compression), dyspnoea (tracheal compression) #@% obstruction etc. 4atural history of simple goiter is given in the bo0. "oiter can be diffuse or nodular Tender goiter can be seen in thyroiditis, bleeding cyst, and tumor. 3eatures suggestive of goiter are 5ain (apid growth %ervical lymphadenopathy %hange in voice

 5ositive 342% In*estigations: T3, T4 and T#' *ltrasound for nodules and cysts %H( for retrostrenal e0tension 342% Thyroid scan) on thyroid scan nodules can be hot (increased upta e) or cold (decreased upta e). 'ot nodules are almost never malignant, but ,;> of cold nodules are malignant. Treatment: +f asymtomatic 7 observe. +f the thyroid functions are abnormal 7treat +ndications for surgery) 5ossibility 5ressure symptoms %osmetic reasons.

THYROID ('R(I&O)'
%lassifications of thyroid malignancies are given the bo0. !ased on cell of origin thyroid malignancies are of various types ,) 5apillary carcinoma and follicular carcinoma) 5apillary carcinoma most common often multifocal and spreads to cervical lymphnodes. 3ollicular carcinoma is always single encapsulated lesion. Metastasis to bone and lung can be seen. Management of both this malignancies is total thyroidectomy followed by +,3,to ablate the remaining thyroid tissue

 5atient should be on thro0ine to suppress the T#'. Thyroglobulin is a good tumor mar er. 'igh levels of thyroglobulin indicate recurrence. 5rognosis is e0cellent for patients below :; yrs and tumor si?e F -cms and confined to lymphnodes. -) 2naplastic carcinoma) 1ifficult to differentiate from lymphoma. Thyroid gland is hard and symmetrical 4o effective therapy. (adiotherapy is for palliation only. 3) Medullary carcinoma) 2rises from the % cells and secretes calcitonin, :'T and 2%T'. #o have features of carcinoid and %ushings syndrome. %ommonly seen in the middle age and goitre if firm. %ervical metastasis is common. %alcitonin is very good tumor mar er. Treatment includes total thyroidectomy with removal of affected lymphnodes. 4o role for + ,3, as % cells will no ta e up the +odine.

(',(I$) )ET'+O,IS)
4ormal levels of calcium are .6,, mg=dl. Metabolism of calcium and 5T' and vit 1 is given the bo0. Parathyroid harmone1PTH/: 5T' is a amino acid harmone secreted from the chief cells of parathyroid glands. 5T' increases the calcium levels in the serum by) 1/ +ncreases the bone resorbtion by increasing the osteoclastic activity. 6/ +n idney it increases calcium reabsorbtion and e0cretion of 5$4. #/ +n idney it converts the inactive form of vit1 (-:vit13) to active form ,,-:vit13. This active vit1 indirectly increases the calcium levels in the body by increasing the vit1 absorption the gut. 4et effect of increased levels of 5T' is hypercalcemia. 'ypophosphatemia and 2&5 is unchanged or marginally elevated.

(al!itonin: 5roduced by the % cells of the thyroid. %alcitonin decreases the calcium levels. +t is very good mar er for the medullary carcinoma of thyroid. 'l aline phosphatase: 2&5 is mar er for the bone formation (osteoblastic activity). #ource of 2&5 can be from bone, liver, idney and placenta.

HYPERP'R'THYROIDIS)
I!auses of hyper!al!emia and hyperparathyroidism are gi*en the "o7. Primary hyper parathyroidism666 increase in 5T' secretion by the parathyroid gland. Se!ondary hyper parathyroidism6666 hyperplasia of parathyroid gland secondary to prolong hypocalcemia. Tertiary hyper parathyroidism88888 adenoma formation and autonomous 5T' secretion of parathyroid gland due to continuous stimulation. (lini!al features: Tiredness, malaise and depression. (enal symptoms) renal colic (due to stones), polyuria, 'T4. !ony pain 5ain abdomen due to peptic ulcer. #ymptoms and signs of underlying cause of hyper parathyroid disease.

 #ome of the symptoms and sings of hyper parathyroidism are given the bo0. In*estigations: #erum calcium and 5$4 and 5T' levels. Mar ed increase in 5T' levels and increase in calcium and decrease in 5$4 levels is typical feature of primary hyperparathyroidism. 2rterial blood gasesDfor acidosis. (enal functions tests and electrolytes. H6ray $steofibrosa cystica666 increased bone resorbtion with fibrous changes and cystic changes. Hray hand showing arrow headed fingers (due to increased resorbtion of terminal phalanges. Hray s ull showing Jpepper potK appearance. Hray abdomen showing renal calculi. +nvestigations for locali?ation *ltrasound of thyroid %T or M(+ Tc.. and Th -;, scan of thyroid and parathyroid followed by digital subtraction by the computer. )anagement: 'ypercalcemia is medical emergency. Management of the hypercalcemia is given the bo0. 80cept for the treatment of hypercalcemia there is not effective medical treatment. #urgery) +ndications for the surgery) 1/ 5atients with renal stones. 6/ #erum calcium E ,,mg>.

#/ Mar ed reduction in cortical bone. 9/ 5ervious severe acute hypercalcemia. #urgery involves removal of adenoma or all 4 glands and implantation into forearm. 5ostoperative complications are same as thyroid surgery. 5ost op. 'ypocalcemia is very common and reCuires replacement. HYPOP'R'THYROIDIS) %auses of hypocalcemia are given in bo0. I Pseudo hypoparathyroidism666 end organ resistance due to abnormal receptor mechanism, associated with short stature and short 4,: metacarpals. : Pseudo Pseudo hypoparathyroidism 666 phenotypic changes li e short stature are present but no hypocalcemia. (lini!al features: %linical features of hypocalcemia are due to neuromuscular irritability and neuropsychiatric manifestations. 5aresthesia, circumoral numbness, cramps an0iety and tetany. %lassical triad in children 666convulsions, laryngeal stridor and carpopedal spasms. (h*oste .s sign;twitching of facial muscles, on gentle taping on the facial nerve. Trousseau.s sign 6666 tetanic spasm of fingers and wrist after inflammation of cuff above systolic blood pressure for 3 minutes. 5apilloedema and basal ganglion calcification. Treatment: 2cute management) 6

 (ebreathing mas reverses al alosis. 3or calcium replacement %a gluconate ,;> ,;ml over ,;minutes. %hronic management)6 @it 1 supplementation, calcitriol (,,-: vit1) orally. 1ose is .-:6 ,microgram per day. 2 commercial preparation of 5T' is ineffective. Treatment of cause of hypocalcemia. +n primary hypoparathyroidism treatment is life long.

HYPOPIT$T'RIS)
(egulation and harmones secreted from pituitary gland are given in the bo0. 3or harmone deficiency diseases stimulatory tests are done. 8.g 2%T' stimulatory test. 3or harmone e0cess disease suppression tests are done. 8.g de0amethasone suppression test. @arious causes of hypopitutarism are given in the bo0. (lini!al features: #ummary of the clinical features, both local and features due to harmone loss are given the bo0. There is always seCuential loss of harmones in order "', 3#'=&', 2%T', T#'.

 %auses of coma in hypopitutarism 1/ 'ypoglycemia 6/ 'ypothermia #/ Gater into0ication 5osterior pituitary harmones are not commonly deficient but can be seen as post operation complications. In*estigations: '/ Harmone e*aluation: 2ll harmones secreted by the pituitary gland are reduced e0cept prolactin(due to lac of dopamine inhibition) 1/ 2%T'Dshort acting 2%T' stimulatory test. 6/ 3#'=&'DMale) random testosterone, &'=3#' 3emale) premenopausal D menstrual history 5ost menopausal 666 3#' and &' 3)T#'666 T3,T4,T#' levels. 4)"' 666 "' levels after 80cersise or insulin induced. !) lo!ali<ation ) @isual field charting. %T=M(+ of the pituitary gland. )anagement: '/ '!ute management: +nj. 'ydrocortisone ,;;mg +.@ A<'rly until patient is stable. Management is same as addisonion crisis. +/ Harmone repla!ement: 1/ (ortisol: $ral hydrocortisone ,;6,:mg in morning and :6,; mg in the evening or prednisolone :mg and -.: mg respectively. Mineralocorticorticoid replacement is generally not reCuired. 6/ Thyroid harmone:

 $ral thyro0ine :;6,;; micrograms per day. 3ollow up is not with (#' but with T4 levels. 2im is to eep T4 high normal. #/ Se7 harmones: #e0 harmones are indicated for men of all ages and premenopausal females if they want normal se0ual function. Testosterone can b given in +M depot preparations(-:;6:;;mg once in -64 wee s), or oral(4;6,-;mg !1) or #=% once in < months. 9/ 0ro=th harmone: (eplacement of growth harmone is reCuired for all young patients. +n adults it can be given to improve sense of well being. +t is given in subcutaneous preparations.

(R'&IOPH'RY&0IO)'
!enign tumor in the rath e/s pouch with cystic changes. $ccurs in the younger patients. %linical features are that of hypopitutarism. #urgery is the treatment but not curative. (ecurrence is very high.

SHORT ST'T$RE
(auses: "rowth is influenced by many factors li e genetic, nutritional etc. @arious causes of short stature are given the bo0.

(lini!al features: 5roper general and systemic e0amination is very important. 80amination of the genitalia and hair. 'eight of the parents along with social and family history. %harts using standard deviation can do assessment of the growth. 80pected height !oys 666 maternal L paternal heightL:inches "irls 666 maternal L paternal height6:inches In*estigations: +nvestigations are mainly done to rule out systemic or endocrine disorders. %ommonly done investigations are "', T3, T4, T#', 'b, (3T, &3T and %H(. Hray of the non6dominant hand can test bone age of the patients )anagement: Treat the systemic causes and endocrine disorders can be treated by replacement of the harmones. $ral estrogens in girls and ing Testosterone in boys can induce puberty in children with constitutional delay in puberty. (ole of growth harmone in Jshort normalK children is doubtful but high doses of "' can be useful in turners syndrome.

These are generally chromophobe microadenomas (F,;mm). @arious causes of hyperprolactinomas are given in the bo0. (lini!al features:

PRO,'(TI&O)'

 %ardinal features of prolactinomas are galactorrhoea (lactation in non6pregnant women) and hypogonadism. +n females features can be amenorrhoea, menorrhagia and infertility. +n males features can be loss of libido, erectile dysfunction. Males present later than females, so they have increased chance of having macroadenoma. Macroadenoma clinical features are already discussed. In*estigations: +n all cases prolactin levels will be increased, but levels more than :;;;m*=l are highly suggestive of polactinoma, as increased levels can also be seen due to drugs, pregnancy and lactation. T3, T4, T#'. 3or macroadenoma investigations are same as hypopitutarism. )anagement: '/ )edi!al: Medical management is first line of management. +n all most all cases medical therapy normali?es the prolactin levels and returns the gonadal function. 1rugs will even reduce the si?e of the adenoma. 1etails of the drugs are given in the bo0. +f the gonadal functions are abnormal despite the normal levels of prolactin then thin of a) associated "n(' deficiency b) menopause. 1uration of the treatment is long 2) +n microadenoma can try stopping the drugs after ,; yrs if there is no recurrence. !) Macroadenoma drugs can be stopped only after surgery.

 +f after staring the treatment patient becomes pregnancy if confirmed treatment should be stopped in microadenoma and care full monitoring + reCuires and in case of macroadenoma drugs should be continued. +/ Surgery: +ndications of surgery are a) %ystic macroadenoma. b) +ntolerance to drugs. %ommonly done surgery is transshenoidal surgery. (/ Radiotherapy: (T is used only for macroadenoma of there is recurrence after surgery.

'(RO)E0',Y
2cromegaly is caused by acidophilic macroadenoma (E,;mm). (lini!al features: 80cess of growth harmone before epiphyseal closure causes gigantism and after fusion causes a!romegaly. %linical features are given the bo0. In*estigations: 2cromegaly is confirmed by doing "' levels after oral glucose tolerance test. 4ormally there will be suppression of the "' levels after oral glucose but in acromegaly there will be no suppression or may be increase in levels. %lonoscopy rule out colonic neoplasm/s( there is increased incidence of colonic neoplasm/s in acromegaly) +"36, levels $ther investigations are same hypopitutarism.

)anagement: a/ Surgery: #urgery is the first line of management. Transshenoidal resection is done. "/ Radiotherapy: This is second line of management. *sed after surgery to stop tumor growth and reduce the levels of "'. There is increased ris of hypopitutarism with (.T. !/ )edi!al therapy: 1rugs are used only if patient has persistent acromegaly even after surgery. 1rugs don/t reduce the si?e of the tumor 1rugs used are 1/ Somatostatin analogues) #omatostatin inhibits the "'. $ctreotide this is given 7+M ing. $nce in -63 wee s 6/ Dopamine agonists #/ 0H re!eptor antagonists: pegvisomant.

DI'+ETES I&SIPID$S1DI/
5osterior pituitary dysfunction is uncommon than anterior. 1+ is commonest disorder of posterior pituitary. +t is due to 21' deficiency. 4ormal thirst regulation is given the chart. (lini!al features: characteri?ed by polydipsia and polyuria(,;6,:l=day)

 +f the thirst mechanism is lost then patient may present with unconscious and with features of dehydration. 2ny patients with polyuria rule out diabetes mellitus and primary polydipsia. In*estigations: +ncreased in serum osmolality (E3;;mosm= g) and decreased urine osmolality (F<<;mosm= g) is very characteristic of 1+. Gater deprivation test 7 given in the bo0. #erum sodium is mar edly increased. #erum 21' levels is not reliable. (ranial DI 7M(+=%T of head and if &ephrogeni! DI is suspected 7 (3T, calcium and phosphate and other renal investigations are reCuired. Treatment: 1esmopressin or 112@5 (1es6amino, 1es2rgininine@asoppressin) is the drug of choice. This drug can be given intranasal (preferred route), oral, +.M( if acutely sic ). +n mild cases thia?ide diuretics, carbama?ipine, chlorpropamide can be used. These drugs increase the sensitivity of the 21' to the @- receptors. Management of the underlying causes.

SY&DRO)E O% I&'PPROPRI'TE '&TIDI$RETI( H'R)O&E1SI'DH/ +mportant and common cause of hyponatremia. %eatures of SI'DH:

1ilutional hyponatremia due to e0cess water. #erum osmolality less than urine osmolality. increased renal sodium e0cretion(E3;mmol=l) 2bsence of volume depletion or edematous states. 4ormal renal, thyroid and adrenal function.

(lini!al features: %onfusion fits coma. 4o features of edema. 3eatures of underlying cause. )anagement: Treatment of the underlying cause is very important. (estrict fluid inta e toB;;6,;;;ml per day. $ral salt ,;6,-gms per day. 'ypertonic saline/s (,.B> or 3>) slow +@ correction. (apid correction causes central pontine myelinolysis. drugs 666 furosamide(osmotic diuresis ) and demeclocycline (diuresis)

'DRE&', 0,'&DS
2drenal glands have a) (orte7;corte0 has two functional parts) ,) >ona fas!i!ular4reti!ularisDsecretes glucocorticoids and androgens -) >ona 0lomerulosa;secretes mineralocorticoids b) )edulla;secrets adrenaline and noradrenalin

 %ontrol of the adrenal glands is given the bo0. 0lu!o!orti!oids: %ortisol is the major glucocorticoids in the humans. %ortisol levels are highest in the morning and lowest in the night. @arious actions of glucocorticoids are given the bo0. )ineralo!orti!oids: 2ldosterone is the predominant mineralocorticoid. 2ldosterone increases the 4aL reabsorbtion and increases 9L and ' Le0cretion. 2ldosterone is important is blood pressure regulation, and is controlled by the (22# system (given in the bo0). 'ndrogens: 2ndrogens are important for puberty. 2ndrogens are regulated by the same '52 a0is. (ate!holamines: $nly small portions of catecholamines are secreted by the adrenal medulla, they are mainly secreted by the nerve endings.

($SHI&0.S SY&DRO)E
Definition: term cushing/s is used to describe the clinical state of free circulating glucocorticoids. cushing/s disease is due to pitutaryadenoma. Types

a) #pontaneous=non iatrogenic b) +atrogenic (lini!al features: Main clinical features are given the diagram. 5atients with ectopic 2%T' secretions have mar ed hyperpigmentation esp. on the tongue lips and hands. %linical features are less common as the patient may not live until full clinical features develop. 'ypo9 L al alosis is common. In*estigations: +nvestigations of cushing/s include tow phases a) %onfirmation of cushing/s syndrome. b) %ause of cushing/s syndrome. @arious investigations done the cushing/s syndrome and flow chart are given the bo0. 5ituitary adenoma causing cushing/s syndrome is almost always is microadenoma. )anagement: 1/ ($SHI&0.S DISE'SE '/ Surgery: #urgery is the first line of management in %ushing/s disease. Transsphenoidal resection of the tumor is preferred method. +f the surgery fails the bilateral adrenalectomy is done. This surgery increases the ris of aggressive pituitary macroadenoma (4elson/s syndrome). 4elson/s syndrome can be treated with pituitary irradiation +/ )edi!al:

 2ll the patients should be treated with drugs before the surgery to control the levels of the steroids. drugs used in the treatment of cushing/s are 1/ MetyraponeD,,hydro0ylase en?yme inhibitor. 6/ aminoglutethimide #/ 9etocona?ole. (/ Radiotherapy: *nli e in adults %ushing/s disease responds very well to (.T in children. 6/'DRE&', ('$SES 'denomaDmedical therapy followed by resection of the adenoma. (ar!inomaDdebul ing surgery or=and (.T. prognosis is poor. #/ E!topi! '(TH: Treatment of the primary tumour.

I'TRO0E&I( ($SHI&0.S SY&DRO)E

%ommonest cause of cushing/s syndrome. @arious indications for steroids and their side effects of steroids are given the bo0. #everity of steroid side effects depends on duration, dose and route of administration. "enerally less than 3wee s therapy or dose F,;mg will not suppress the '52 a0is. @arious eCuivalent doses of steroids are given in the bo0. 5oints to be remembered during steroid therapy.

1/ &ong6term steroid therapy should never be stopped suddenly, should be tapered slowly and then stopped. J2lternate dayK regimen can be used. 6/ 1oses should be increased during serious intercurrent illness. #/ 5atient should be informed of the side effects.

'DDISO&.S DISE'SE
(lini!al features: %linical features of the !hroni! 'ddison.s disease given the diagram. clinical features of a!ute 'ddison.s disease are) 1/ unconsciousness 6/ %irculatory shoc with hypotention. #/ @omiting and diarrhoea. In*estigations: Short a!ting '(TH stimulation test) -:;microgms of 2%T' are injected +.@. serum cortisol levels are chec ed at ;,3; and <; minutes. 4ormal response is increase in serum cortisol levels more than <;;mmols=l or increase by 33;mmols=l.lac of normal response confirms the diagnosis of 2ddison/s disease. +f the short acting test is not conclusive then long a!ting '(TH stimulation test is done. +n this test cortisol is tested ;,,,-,3,4,:,B,-4 hrs intervals. '(TH le*els;done early morning. increased in the 2ddison/s disease. 'ldosterone and renin: these tests are done supine position. +n 2ddison/s disease aldosterone is decreased and renin is increased. 'ypoglycemia, hyponatremia, and hyper alemia. 2drenal antibodies.

 %H( (for pulmonary T.!), %.T abdomen. )anagement: &ong6term replacement therapy of glucocorticoids are reCuired, rarely mineralocorticoids are also reCuired. (eplacement doses and advice to patient of 2ddison/s disease is given in the bo0. 1oses of the drugs adjusted based on clinical improvement and cortisol and 4a and 9 levels. )anagement of a!ute hypoadrenalism: 1/ +.@ fluids) one liter of 4#=,;> de0trose in first one hour and then several liters there after. 6/ +ng. hydrocortisone ,;;mg +.@ stat and then repeat A<hrly until patient can ta e orally. #/ 3ludrocortisone is not reCuired. 9/ Treat the precipitating cause esp. infection with antibiotics. (O&0E&IT', 'DRE&', HYPERP,'SI'1('H/ $ne of the important cause of hypoadrenalism. %2' is autosomal recessive disorder, deficiency of en?ymes of cortisol synthesis. %ommonest deficiency is -,hydro0ylase resulting in reduced levels of cortisol and increased of 2%T'. (lini!al features 1/ %emales) ambiguous genitalia, clitoromegaly and hypoadrenalism. 6/ )ales: enlarged penis and increased pubic hair and hypoadrenalism. #/ 1eficiencies of ,, hydro0ylase and ,M hydro0ylase present with hypertension. In*estigations:

 (educed levels cortisol and increased levels of ,M hydro0yprogesterone and 2%T'. $ther investigations are same as 2ddison/s disease. )anagement: (eplacement of glucocorticoids is the main stay therapy. aim is to suppress the 2%T'. 1oses of steroids are same as addisons but higher dose is reCuired in the night and lower in the morning

PRI)'RY HYPER',DOSTERO&IS)
4ormal regulation of (22 system and various causes of mineralocorticoid e0cess are given in the bo0.

(lini!al features: 'ypertension is the most common presenting symptom. 5atients may also present with complications of hypertension li e M+, stro e etc. 5olyuria (due to nephrogenic 1+) and tetani (due to al alosis). Muscle wea ness (due to hypo alemia) especially in %hinese. 5eripheral edema is very rare. In*estigations: 'ypo alemia and al alosis are the typical changes. #odium is in high normal range. 5lasma aldosterone and renin activity is increased and levels of renin will be decreased and aldosterone will be increased. 2ll antihypertensives should be stopped before measurement of renin and aldosterone as they interfere with the measurements. &ocali?ation of the tumor is by %T abdomen. )anagement: ,) %onn/s disease (adenoma) *nilateral adrenalectomy is the treatment of choice. Medical therapy with spiranolactone is must before the surgery to normali?e the electrolytes. +f the hypertension persist after the surgery then continue the spiranolactone. -) +diopathic hyperplasia) Therapy is with spiranolactone 2drenalectomy is not indicated.

PH'EO(HRO)O(YTO)'
5haeochromocytoma is a tumor of chromaffin cells, which secretes catecholamines. Rule of tenD,;> malignant, ,;> e0traadrenal, ,;> familial. (lini!al features: Major features are given in the bo0. May present with complication of hypertension li e stro e, M+, &@' etc. (arely may be associated with M84 ++ a (details of M84 are given the bo0), vonhippel6lindau syndrome. In*estigations: 2) !iochemical) -4 hr collection of urinary @M2 (vallinyl mandelic acid) and catecholamines. #erum levels of @M2 and catecholamines are not reliable as the substances are secreted paro0ysmal. +ncreased levels of the substances can also occur with patients on antihypertensive drugs li e betablo ers, so these drugs have to stopped before measurement of catecholamines. clonidine normally suppress the catecholamines but in 5haeochromocytoma it does not suppress(so this will be ideal antihypertensives drug during the investigation of 5haeochromocytoma)

!) &ocali?ation) %T abdomen 80tramedullary by meta6iodoben?y "uanidine (M+!") labeled scan.

)anagement: 1/ )edi!al therapy: Medical therapy should be given for atleast for <wee s before surgery. 5heno0yben?amine is the preferred drug. +t is non6selective alpha blo er. +f there is e0cess tachycardia then beta blo er li e propranonol can be used. 4ever use betablo ers alone as unopposed alpha action may rapidly increase the blood pressure. 1uring the surgery sodium nitroprusside can be used. 6/ Surgery: Treatment of choice6resection of tumor. +f surgery is not possible then medical therapy alone.

DI'+ETES )E,,IT$S

Def: #yndrome characteri?ed by chronic hyperglycemia and relative insulin deficiency, resistance or both. Gorldwide prevalence of the disease is about ,-; million. prevalence in +41+2 is about is about ,36,4 >. 0,$(OSE )ET'+O,IS): &iver is the principle organ for regulation of glucose metabolism. &iver stores the glucose in the form of glycogen. This glycogen is released whenever it is reCuired. &iver also produces glucose by gluconeogenesis (from proteins, fat, and muscle glycogen). "lucose reCuired per day is about -;;mg, :;> of this glucose if utili?ed by the brain (insulin is not reCuired for the glucose utili?ation in brain). $ther major sites of glucose utili?ation are muscle and fat. +nsulin is the major harmone regulating the glucose metabolism. insulin reduces the blood glucose levels. 2drenaline, glucagon, cortisol, and growth harmone counter regulate insulin actions. "lucose is transported into cells by specific glucose transporter protein ("*&T). "*&T is of 4 types. ,. Type , seen peripheral cells and don/t reCuire insulin. -. Type - seen in beta cells. 3. Type 3 seen in brain. 4. Type 4 seen in the peripheral tissues and reCuire insulin for glucose upta e

Insulin:

 #tructure of the insulin is given the bo0. +nsulin is coded on chromosome number ,,.

+nsulin is secreted from beta cells of pancreas 5ortal circulation

2ction on the liver and peripheral tissues

3inally metaboli?ed in the liver and idney

%6peptide is also secreted along with insulin from the beta cells. !ut %6peptide is not fully metaboli?ed. #o levels of %6 peptide can be used for differentiate type ++ from type +. Major actions of +nsulin areDnet effect is reduction in the levels of glucose. Inhi"its "luconeogenesis "lycogenolysis &ipid and protein degradation 9etogenesis Promotes "lucose upta e by the peripheral tissues "lycogenesis 5rotein and fat synthesis

Pathophysiology of the type 1 dia"etes mellitus:

Etiology 1/ 0eneti! Type , 1M has 5olygenetic inheritance. '&2 1(3 and 1(4 increase the susceptibility. %hromosome ,, abnormalities are also lin ed. $nly 3;6:;> of the identical twins have type , 1M. 6/ 'utoimmune: Type , 1M is immune mediated disease as it is commonly associated with other autoimmune disorders li e pernicious anemia, thyroiditis, vitiligo etc. Mechanism of autoimmune mediated destruction of beta cells is given the bo0. These auto antibodies are seen well before the clinical development of diabetes. Pathophysiology of type 6 dia"etes mellitus: Etiology 1/ 0eneti! ,;;> of the homo?ygous twins develop type- 1M (so very strong genetic influence) 6/ En*ironmental fa!tors ,ife style;overeating and obesity 'ge 888 as the age advances ris of type - 1M increases. 2bout ,;> of the population above <: years are diabetic. Pregnan!y ?gestational diabetes increases the chance of type- 1M )alnutrition : Major risk factors for developing type !M are given in the bo". #hese people have to be screened for type !M.

Pathogenesis: ,. +nsulin resistance. %ause of insulin resistance may be abnormal receptors, increased antagonists or abnormal insulin. -. #econdary failure of beta cells. 3. +nsulin resistance syndrome or metabolic H6syndrome or (eavens syndrome666 increased ris for atherosclerosis. )aturity Onset dia"etes of Young 1)ODY) 2utosomal dominant inheritance. #trong family history (more than 3 generations) M$1N is due to genetic mutations causing abnormal !eta cell function. %onstitute ,: of all diabetics and commonest verity is gluco inase gene defect. $ther verities are given the bo0. %i"ro!al!ulous Pan!reati! Dia"eti! 1%(PD/ %ommon in +41+2. $ccurs between -;64; yrs of age. !asic pathology is fibrosis of pancreas with calculi and dilated ducts. 2ny young diabetic, 3%51 has to be ruled out.

DI'+ETES )E,,IT$S1!ont../
(lini!al features: Type1 D) Symptoms: "eneral age of presentation is less than -; yrs. $smotic symptoms li e polyuria, polydyspsia, polyphagia are the presenting features. Geight loss is very common. May present with features of 192. 3amily history of 1M may or may not be present. Signs: &ow !M+ is very characteristic. 8vidence of infection in the form of furuncles, respiratory infections may be present. 8vidence of other autoimmune disorders li e graves, addison/s, vitiligo may be present. Type 6D) Symptoms: %lassical age of presentation is above 4;yrs. May be detected on routine e0amination. 5resenting symptoms may be infections li e vulvovaginitis, balanitis, and pneumonia. 192 as presenting feature is very rare unli e type, 1M. Type-1M unli e type, may present with complications of diabetes.

1/ 5rogressive loss of vision, sudden loss of vision, freCuent change of glasses666dia"eti! retinopathy. 6/ 5edal edema, facial puffiness, and hypertension6666 dia"eti! nephropathy. #/ !urning sensation in the feet and hands isolated cranial nerve palsy, pro0imal muscle wea ness 666 dia"eti! neuropathy. 9/ 8rectile dysfunction, urinary incontinence, nocturnal diarrhoea, giddiness on standing 666autonomi! neuropathy. @/ 3eatures of IHD and (5'. A/ 'istory of claudicationDperipheral vascular disease and foot ulcers 666 dia"eti! foot. 3amily history is generally strongly positive. 5ersonal history 7 history of sedentary life, lac of e0ercise, smo ing, alcohol should also be as ed. +n any case of diabetes already diagnosed as for 1/ Ghen and how 1M was diagnosed. 6/ +s the patient following proper diet and 80cersise. #/ what drugs were prescribed and any side effects(including insulin) 9/ 'ow freCuently sugars are being chec ed. Signs: +)I generally is more than -:(o"esity). Gaist hip ratio E ;... PallorDmay be feature of %(3 due to diabetic nephropathy. ,ymphadenopathy666 may be a feature of occult infection li e tuberculosis. Pedal edema 666 possible causes are nephropathy, %%3, drugs li e amlodipine, pioglita?one. May give clue for cause of diabetes li e steroid induced %ushing/s syndrome etc. Pulse 7 resting tachycardia (autonomic neuropathy), absent peripheral pulses (5@1), carotid bruie and thic ened vessel wall (atherosclerosis). +lood pressure) standing and lying !5 should be ta en in all diabetic patients. $ostural hypotention may be a suggestive of

autonomic neuropathy, side effect of drug li e clonidine, 2%8 inhibitors. 9usssmausal/s breathing may be seen in 192. other general e0aminations features include) 1/ -anthomas and -antholesma.s (feature of hyperlipidemia). 6/ $ral candidiasis, thyroid swelling (thyroiditis as in type ,1M). #/ 3acial puffiness 7 nephropathy, secondary causes li e %ushings syndrome. 9/ '!anthosis nigri!ans 7 velvety pigmentation commonly seen on bac of the nec , a0illa and groin regions. @/ 'ands 7 loo for dupytren/s contracture, carpal tunnel syndrome, and prayer/s sign. A/ &ipoatrophy and dystrophy at the insulin injection sites. B/ Dia"eti! dermopathy (hyperpigmented patches seen on shin) necrobiosis lipoidica (on shin). C/ 3oot for ul!ers on the pressure sites and fungal infections. D/ %harcot joints.

+)I E 6@F =aist hip ratio E G.D and a!anthosis nigri!ans are features of insulin resistance.

(5S: %eatures of IHD ? hyperdynamicape0, #3, dys inatic segment, and M( murmur. 3eatures of 'T4sive heart disease 666 heaving ape0, loud 2-, #4, 8#M in aortic area. '"domen: 'epatomegalyDfatty liver, %%3. 2scitis 7 %%3, nephropathy. 80ternal genitalia for infections (enal bruie.

Respiratory system: basal crepitations666%%3 and fluid over load states li e nephropathy. #igns of pulmonary T!. (&S: 3undus for diabetic retinopathy and hypertensive retinopathy. %ranial neuropathies. Motor system666 lower limb pro0imal muscle wea ness(amyotrophy) #ings of sensory motor neuropathy 7 fine touch (by monofilament), vibration (,-Bh? tuning for ), joint position sensation and rhomberg/s sign, pain sensation by needle. refle0es esp. an le and nee joint. @ibration sensation is the first sensation to be lost in diabetics. #igns of stro e.

$ne micro or macro vascular complication loo for other micro or macro vascular complications. 8.g nephropathy is very commonly associated with retinopathy. 2therosclerosis at one site loo for atherosclerosis at other sites.

%(PD 1%i"ro!al!ulous Pan!reati! Dia"etes/ %ommon age of presentation is -;64; yrs. #ymptoms and presentation is similar to type , 1M but diarrhoea and pain abdomen may be a predominant feature.

,a"oratory %indings +ase line in*estigations to "e done in a patient diagnosed as D) for the first time: 1/ 3!#,55!#, "ly 'b 6/ 'emoglobin. #/ *rea, creatinine, 4a, 9. 9/ *rine for microscopy and albuminuria. @/ 3asting lipid profile. A/ 8%". B/ $ther investigations if reCuired 666 %H( (pulmonary T!) %6peptide (To differentiate type, and type-, increased in type *ltrasound abdomen and 06ray abdomenD3%51.
0ly!osylated H":
'emoglobin becomes glycated by etoamine reactions between glucose and the free amino groups on the and chains. This glycated 'b portion can be measured as 'b 2, . The major form of 'b2, is hemoglobin 2,c ('b2,c). #ince glycohemoglobins circulate within red blood cells whose life span lasts up to ,-; days, they generally reflect the state of glycemia over the preceding B7,- wee s, thereby providing an improved method of assessing diabetic control

#hould never be used for diagnosis but is the best investigation for follow up. +deal value of 'b2,c is less than <.:>. 2n increase in ,> of 'b2,c reflects increase in sugar app0. 4;mg=dl.
2ny condition that shortens erythrocyte survival or decreases mean erythrocyte age (eg, recovery from acute blood loss, hemolytic anemia) will falsely lower 'b2,c Serum fru!tosamine #erum fructosamine is formed by nonen?ymatic glycosylation of serum proteins. serum fructosamine generally reflects the state of glycemic control for only the preceding ,7- wee s
SELF-MONITORING OF BLOOD GLUCOSE

%apillary blood glucose measurements performed by patients themselves, as outpatients, are e0tremely useful. There are several paper strip (glucose o0idase, glucose dehydrogenase, or he0o inase) methods for measuring glucose on capillary blood samples.

CONTINUOUS GLUCOSE MONITORING SYSTEMS

%ontinuous glucose monitoring systems are currently available for clinical use. +t involves inserting a subcutaneous sensor that measures glucose concentrations in the interstitial fluid for M- hours.

)'&'0E)E&T O% D)
There are three modes of treatment of 1M. 1/ 1iet and 80ercise. 6/ $ral hypoglycemic agents ($'2) #/ +nsulin Type of therapy is based on circulating plasma insulin concentration. Therapy of diabetes is for life long. 'ims of the therapy: 1/ 4ear normal glucose metabolism. This includes "ly 'b FM.:,3!#F,,;mg=dl and 55!#F ,4;mg=dl and !5 F,3;=B; and cholesterolF:mmol=l. 6/ To avoid acute and chronic complications. +) Diet and e7er!ise Two types of diets are available 1/ Geight reduction diet666 for obese patients 6/ Geight maintenance diet 666 for lean patients 3or obese patients weight loss of .: 9g per wee should be aimed. Height maintenan!e diet Maintain at -: 4:> 4;> ,M> Height redu!tion diet Maintain at -:;6::> 3;63:> F,;>

!M+ %arbohydrate 3at #aturated fat

M*32 5*32 5rotein

,,> <> ,-6,:>

,;6,:> F,;> ,;6,:>

0ly!aemi! inde7;it is ratio of glucose level after ta ing a particular food to that of glucose of same Cuantity. 3oods of low glycaemic inde0 are preferred. 3iber rich diets (cellulose, pectin of plants) are advised as they reduce rapid swings of glucose levels. +ndian food is rich in fiber. 2ttention should be paid for the type of fat ta en by the patient. 2rtificial sweeteners (saccharin and aspartamate) are available but costly alternative. 3resh fruits can be ta en but not juices. 2void alcohol and smo ing. (educe salt inta e to less than <grms per day if patient has hypertension. E7er!ise: +t improves glycaemic control by reducing insulin resistance, body weight and ris factors for %21 2erobic e0ercises li e wal ing, swimming and cycling are better. !ris wal ing for ,=-hr=day is sufficient. 5atients on insulin should have snac s before strenuous e0ercise. Oral hypogly!emi! agents 1OH'/ '/ Sulphonyl ureas 1S$/: M.$.2 6666 ,) #timulate beta cells to release insulin. -) 1ecrease hepatic release of glucose. %ommon drugs

,) 3irst generation 7 Tolbutamide, %hlorpropamide. -) #econd generation 666 glicla?ide, glipi?ide (:mg), glibenclamide (:mg, -.:mg), glimepiride (,mg, -mg). These drugs are generally given before food. These drugs should be used with caution in liver and renal disorders. #* are not preferred drugs in obese patients as they can cause weight gain. Side effe!ts) 1/ 'ypoglycemiaDmore common with than second. "libenclamide should be avoided in elderly patients, as chance of hypoglycemia is very high. 6/ %holestasis #/ 1ilutional hyponatremia. #* have interaction with aspirin and alcohol. #ome patients may fail to respond to #* 7 Jprimary failureK while some patients may initially respond but later are unresponsive 7 Jsecondary failureK. These patients will respond to other group of drugs or insulin. +/ +iguanides M.$.2 66 ,) +ncrease peripheral upta e of glucose. -) +mpairs glucose absorption from gut. 3) +nhibit gluconeogenesis. 8.g phenformin, metformin. 1ose (metformin) :;;=B:;mg T+1 or :;;=,;;;mg sustained release preparations can be given $1 or !1. These drugs should be given after food. These drugs are contraindicated in liver and renal failure, heavy alcoholics and patients with active infections. Side effe!ts ? ,) &actic acidosis. -) 2nore0ia, nausea, vomiting. 3) Metallic taste

 These drugs are preferred drugs in obese patients as they cause weight reduction. $ther uses of metformin are 5%$1, obesity, 42#'. (/ 'lpha8glu!osidase inhi"itors M.$.2 7 inhibit disaccharidases in the gut and delay carbohydrate absorption. 8.g 7 2carbose, maglitol. 1ose (acarbose) 7 :;mg T+1 with each meal. #ide effects 7 flatulence, abdominal bloating and diarrhoea. D/ Thio<olidinediones: M.$.2 7 increases insulin sensitivity on the peripheral tissue esp. fat. 8.g rosiglita?one, pioglita?one. 1ose 7 pioglita?one ,:=3;mg $1. #ide effects 7 pedal edema, weight gain, head ache and fatigue. %ontraindicated in cardiac failure and congested states. D/ )eglitinides: M.$.2 7 same as #* but receptor is different. 8.g 7 repaglinide, nateglenide 1ose (repaglinide)66 ;.:6, mg T+1. #hould be ta en with meals. These drugs regulate postprandial sugars very well. #ide effects are very similar to #* but hypoglycemia is very rare. (om"ination of *arious OH' +f the patient sugars are not controlled by single drug then combination of drugs can be used for regulation of sugars. %ommonly used drug combinations are ,) #* and Metformin. -) #* and 5ioglita?one.

3) Metformin and 5ioglita?one. +nsulin can be added to and of these combinations if the sugars are not undercontrol. Insulin: 5reviously insulin was manufactured from pancreas of cow and pigs. !ut now human insulin is manufactured by 142 recombinant technology, faster and cheaper. !ased no the duration of action of +nsulin/s can be classified into 4 groups as given the bo0. #hort acting insulin/s (clear solutions) duration of action can be e0tended by added protamine or ?inc (lente) or both (45' and isophane). +nsulin is injected subcutenously and various sites of injection are given the diagram. +nsulin can be given intravenously or intramuscularly in emergencies li e 192. 4ow insulin pumps are also available. +nsulin syringes are available in two strengths 74;+*=ml and ,;;+*=ml.thes needle strengths should match that of insulin vials. 4ow premi0ed combination short acting and intermediate acting insulin/s are available 7 :;=:; or 3;=M;. @arious regimens of insulin combination are to maintain stable levels of insulin in blood and to prevent hypo and hyperglycemia are given the bo0. 5atient education about +nsulin, its side effects and method of administration is very important. #ide effects of insulin are given the bo0. Insulin analogues 1/ !y changing the seCuence of aminoacids in the +nsulin acting of the insulin can be modified, these modified insulin/s are called insulin analogues.

6/ *ltrashort acting 666 lispro insulin and 2spart #/ &ong acting 666 "largine 9/2minoacids seCuence changes in these insulin/s are given given the bo0. @/These insulin/s have same biological activity as human insulin/s but pharmaco inetics are more suitable.

+ndications of insulin therapy are a) &ong term Type ,1M Type- 1M with failure of $'2 b) +ntermittent Type- during infection Type- 1M during surgery Type- 1M 7 M+ and stro e. 192 and '49% 5regnancy $ther uses of insulin are 666 hyper alemia and stimulatory tests for endocrine disorders li e acromegaly. 4on6diabetic uses of insulin are 7 hyper alemia, stimulatory tests in growth harmone abnormalities. Somoyogi effe!t) This phenomenon is due to late night hypoglycemia followed by early morning hyperglycemia. This can be confirmed by low glucose levels at 3 am. %ause 7 high dose of insulin in the night. Treatment 7 reduce the dose of night insulin. Da=n phenomenon:

 This phenomenon also causes high 3!# but there is no 3 am hypoglycemia. %ause 7 increased counter regulatory harmones li e "'. Therapy 7 increase the night dose of insulin or delay the night dose to .6,; p.m. 3ollow up of diabetic patient is given the bo0.

'($TE (O)P,I('TIO&S O% D)
2cute complications of 1M include 1/ 1iabetic etoacidosis (192) 6/ 4on etotic hyperosmolar coma (49'%) #/ 'ypoglycemia. 9/ &actic acidosis DI'+ETI( IETO'(IDOSIS 1DI'/ 192 is medical emergency and mortality is about :6,; >. %ardinal features are 1/'yperglycemia 6/'yper etonemia #/Metabolic etoacidosis 5athophysiology is given the bo0. 5recipitating factors +nfection #urgery Trauma M+ and %@2

1rugs li e %orticosteriods 8motional stress 9etones produced are beta hydro0y butyric acid, acetone and acetoacetate. 192 can cause fever, leucocytosis even without infection. %linical features, diffencial diagnosis and management and compilations of 192 are given the bo0. 2ll patients of 192 initially have normal or high 9 but with insulin therapy 9 is reduced.

9 replacement E :.: mmol=l 7 no 9%l 3.:.:.: mmol=l 7 -;mmols per liter of fluids F3.: mmol=l 7 4;mmols per liter of fluids &on etoti! Hyperosmolar !oma 1&IH(/ 49'% is characteri?ed by severe hyperglycemia and with or without significant etoacidosis. More common in elderly and mortality is about :;6B;>. @arious differences between 192 and 49'% are given the bo0. #ome useful formula/s in 192 and 49'% 1/ Serum osmolality ? -(4a L9) Lurea=:.< Lglucose=,B.normal serum osmolality is -B;63;; mosmols= g 6/'nion gap 7 (4a L 9) 7 (%l L '%$3). 4ormal anion gap is ,;6 ,-. 2" is mar edly increased in 192 but normal to high in 49'%. )anagement: Management of 49'% is same as 192 with some differences

1/ 49'% is very sensitive to insulin so half the dose of insulin is used. 6/ #hould use .4:> of 4a%l until serum osmolality is normal then normal (..>) saline can be used.

I 'ypoglycemia is dealt in detail later. I &actic acidosis in diabetic patients can be caused due to infection or metformin.

(HRO&I( (O)P,I('TIO&S O% D) '/ )i!ro*as!ular !ompli!ations 1/1iabetic retinopathy 6/1iabetic nephropathy #/1iabetic neuropathy including autonomic neuropathy +/ )a!ro*as!ular !ompli!ations 1/%@2 6/+'1 #/ 5eripheral vascular disease(5@1) (/ Others 1/ 1iabetic foot 6/ 1iabetic dermopathy #/ (heumatalogical manifestations of 1M. (details are already mentioned in clinical features). 9/ 1yslipidemia

Dia"eti! nephropathy 1iabetic nephropathy is the most important cause of 8#(1 all over the disease. @arious stages of diabetic nephropathy are 1/ #tage of hyperfiltration 6/ #tage of microalbuminuria(3;63;;micrograms of albumin=day) #/ #tage of overt proteinuria. 1uring this stage patient may have nephrotic range of proteinuria. 9/ 8nd stage renal disease(8#(1) 5attern of progression of diabetic nephropathy is given the bo0. 5athological changes include thic ing of glomelular basement membrane and later nodular deposits with glumeruloscerosis (9immelsteil6wilson lesion). 9immelsteil6wilson is very typical of diabetic nephropathy. (lini!al features of diabetic nephropathy 7 pedal edema, facial puffiness, pleural effusion, ascitis 8tc. In*estigations 1/ *rine for microalbuminuria 7 details are given the bo0. 6/*ltra sound abdomen to rule out obstructive uropathy and other causes of renal failure. #/(enal functions and electrolytes. 9/ +nvestigations to rule out other complications. )anagement: 1/2ggressive control of !5. Target !5 should be below ,-;=B;. 1rug of choice for diabetic nephropathy with or with out hypertension 666 2%8 inhibitors or 2(!/s. (ead about various 2%8 inhibitors and 2(!/s with their side effects.

 These drugs not only reduce the !5 but also reduce the proteinuria. These drugs are contra indicated in presence of renal failure. 6/Tight control of sugars. 2void using metformin if there is renal failure. +ncidence of renal failure, dose of insulin will come down mar edly. 3) #creen for diabetic retinopathy and other complications. 4) 2void nephroto0ic drugs and treat *T+. @/(enal replacement therapy is reCuired for patients with 8#(1. These include dialysis and renal transplantation.

Dia"eti! neuropathy
8ffects 3;> of diabetics. 5athogenesis includes a0onal degeneration and damage to vasa nervosum. %lassification is given the bo0. (lini!al features 1/ #ymmetrical sensory polyneuropathy) 5arathesia of feet and hands (glove and stoc ing distribution). Muscle wasting and wea ness are late features. #ensory loss and loss of 1T( are the main features. @ibration sensation (,-B'?) is the first sensation to be lost. May develop foot ulcers(diabetic foot) and charcot joints) 6/2symmetrical diabetic motor neuropathy) %alled as diabetic amyotrophy. %auses progressive wea ness and wasting of pro0imal muscles. Gea ness is asymmetrical and painful. !ut prognosis is good.

#/Mononeuropathy) #ingle peripheral nerve palsy. May mimic hensen/s disease. %ranial nerve palsies are also common esp. 3rd and <th nerves. Thoracic nerves can also be affected. %arpaltunnel syndrome can also be feature of 1M. 9/2utonomic neuropathy) @arious features of autonomic dysfunction are given the bo0. 8rectile dysfunction is also very common. )anagement of neuropathy "iven the bo0.

DI'+ETI( %OOT Etiology: Trauma (trivial) in presence of neuropathy and 5@1 666ulcer and infection. 4europathy or ischaemia or both can cause diabetic foot. %linical features and management of diabetic foot are given the bo0. (ead diabetic retinopathy.

%21, 5@1 and %@2 are described in detail in corresponding chapters.

S$R0ERY '&D DI'+ETES 2ll patients undergoing surgery 666 catabolic stress leading to cortisol and catecholamines and glucagon. These harmones increase glucose levels and increase insulin resistance and predispose the patient to 192 esp. if the sugars are uncontrolled before the surgery. +ncrease in glucose levels also delays the wound healing, so increase the post operation complications. 1etails of the management of the patient before and during the surgery are given the bo0. PRE0&'&(Y '&D DI'+ETES '/ Pregnan!y in a dia"eti! patient. *ncontrolled sugars during pregnancy can cause fetal abnormalities and increase in the perinatal mortality rate. Management of the diabetics during pregnancy is given the bo0. +/ 0estational dia"etes 1ef) 'yperglycemia diagnosed first time in pregnancy. (is factors 1/ age E-: 6/ !M+ E-: #/ 5ast history of gestational diabetes. 9/ family history of 1M 2ll pregnant women who are at ris should be screened. Testing for "1M should be done between -46-Bwee s. T=o step method 1/ Step one: :;gms of oral glucose (any time of the day). Then venous plasma sugars after one hour.

 4ormal F,4;mg>O if the value is E,4;mg> proceed to step two. -) Step t=o: Bhrs of fasting 888 ,;;gms of glucose orally then draw plasma venous sample at ;,,,-,3 hrs. - or more abnormal values 7 diagnostic of "1M 1/ fasting 7 .: mg=dl 6/ ,hr 66 ,B; mg=dl #/ -hrs 666 ,::mg=dl 9/ 3hrs 666 ,4;mg=dl )anagement: 5lan early delivery 7 3<63Bwee s due to increased ris of +*1. 2void $'2 and control the sugars by insulin. Maintain the sugars below ,;:mg=dl. $n the day of delivery stop insulin and start glucose and insulin and 9 infusion and monitor sugars -63 hrs. Maintain the sugars between .;6,,; mg=dl. 3ollow6up of the patients with "1M is very important, as they have increased ris of developing 1M. HYPO0,Y(E)I' DE%: %linical state associated with low glucose levels (F:;mg=dl) or relatively low plasma glucose levels associated with sings and symptoms of autonomic and neuroglycopenic symptoms. %ommon causes , clinical features and conditions mimic ing hypoglycemia are given the bo0. 5ostprandial hypoglycemia is seen in6patients who have undergone "P surgery and have complications li e dumping syndrome. Hhipple.s triad :

1/ 'istory of hypoglycemic symptoms. 6/ !lood glucose levels than 4;mg=dl. #/ +mmediate recovery upon administration of glucose. (elation of blood sugar levels and symptoms) ,. &ess than M;mg=dl 7 increase in "' and "lucagon -. &ess than <;mg=dl 7 2utonomic symptoms and increase in cortisol. 3. &ess than :;mg=dl 66 4euroglycopenic symptoms %auses of hypoglycemia in a diabetic patient) 1/ 80cessive dose of insulin or $'2/s. 6/ Missing the meals #/ Mismatched vials 9/ 80ercise @/ 2lcohol inta e A/ (enal failure B/ #epsis +nsulinoma diagnosisDGhipple/s triad with high levels of insulin. Hypogly!emia una=areness 7patient with long6term diabetes and with neuropathy may not develop hypoglycemic symptoms until sugars reach very low levels. They present directly with neuroglycopenic symptoms. 'ypoglycemic unawareness is common with diabetics who are over treated. These patients are prone for recurrent hypoglycemia. )anagement: 'ypoglycemia with altered sensorium should be treated with :;6,;;ml of :;> de0trose +@ over ,6- mins. 3or milder cases oral sugar can be given. +ng glucagon ,mg +@ can also given. 2voiding the precipitating factors is also very important li e, s ipping of food after ta ing insulin, long acting $'2 etc. 5ostprandial hypoglycemia can be treated with anticholenergic drugs to prevent rapid emptying of food.

 +nsulinoma 7 surgical resection is the curative therapy. +n6 patients who have metastasis can be treated with glucagon for emergency situations, or oral dia0oide can be used. $ctreotide can also be used. +n a diabetic patients with hypoglycemic symptoms) 1/ #top all #* and insulin. 6/ 2fter treatment adjust the insulin doses. #/ &oo for renal failure. 9/ 2dvice patient to carry sugar containing food always with him. 5atient education about the hypoglycemic symptoms and about the disease esp. diabetic is very important.

)',E HYPO0O&'DIS)
Def) +nadeCuate gonadal function. (auses and !lini!al features of male hypogonadism are given the bo0. In*estigations: Testosterone, &' and 3#' levels. +n primary gonadal dysfunction testosterone decreases and &' and 3#' levels increase. +n secondary gonadal dysfunction all 3 harmones levels fall. M(+ and %T scan for wor up of secondary gonadal dysfunction. &T3 and (3T etc to rule out systemic diseases.

 )anagement: (eplacement) primary causes 666 testosterone #econdary causes 666 &', 3#' or pulsatile "n('. Testosterone enenthate -:;mg +M every 3 wee s or testosterone undecanoate B;6-4;mg per day oral. ERE(TI,E DYS%$&(TIO& DE%) consistent inability to maintain an erect penis with sufficient rigidity to allow se0ual intercourse. (auses) 1/ 2rterial 6/ @enous #/ 4eurogenic 9/ 5sychogenic &oss of libido suggests reduced androgens. (etrograde ejaculation may be due to bladder nec problems. (lini!al features) 1/ diffenciate from ejaculation and libido. 6/ 'istory of 1M, 'T4 and drugs esp. li e beta6bloc ers and trauma. #/ $n e0amination loo for secondary se0ual characters, peripheral pulses and motor and sensory e0amination. Management) 1/ Testosterone replacement if there is loss of libido. 6/ @acuum constriction device for venous disorders. #/ @asoactive therapy 7 sildenafil and prostaglandin/s. 9/ 5enile prosthesis. @/ @ascular reconstruction/s for arterial disorders. Read 'menorrhoea and gyna!omastia.

,IPID '+&OR)',ITIES
2polipoproteins maintain structure of various lipid particles and also help in their metabolism. 8.g !,;;, ! 4B. '1& protects from %21 by J reverse cholesterol transportK by the help of the en?yme &%2T ( lecithin cholesterol acyl transferase) (lassifi!ation: 3redric son classification is very complicated. 'e has divided lipid abnormalities into : groups. 5ractical classification is given the bo0. (lini!al features: 2symtomatic, and accidentally detected due evaluation of 1M, 'T4 or %21. 5atient may present with pancreatitis esp. familial hypertriglyceridemia. Hanthomas 7 on 2chilles tendon, platella and bac of hand. Hantholesma 66 deposits around eye esp. upper eye lid. 8ruptive Hanthomas 7 over buttoc s seen esp. in &5& deficiency patients. %orneal arcus. 2ny patient who has presented with early onset of %21 suspect familial lipid abnormalities. Most of the signs given above are more common in familial variants than secondary causes. In*estigations: 3asting lipid profile (3&5) 7 T.chol, '1&, T".

Q &1& cholesterol R Total cholesterol6('1& LT"=:) (ule out secondary causes 7 sugars, &3T, T3T, urine protein, (3T. 2s for history of inta e of drugs li e beta6bloc ers. )anagement: '/ Diet 2ll patients should have a trial of diet before the starting drugs for management of hyperlipidemia. 1etails of the diet therapy are given the bo0. +/ H)0 (o Redu!tase Inhi"itors 1statins/ E.g #imavastatin (:6,;mg) 2torvastatin (:6,;mg). M.$.2 7 +nhibits cholesterol synthesis. #ide effects 7 increase in liver en?ymes, Myositis. %.+ 7 pregnancy and lactation and liver disorders. (/ %i"ri! a!id deri*ati*es: 8.g "emfibrocil, finofibrate, !en?afibrate. M.$.2 7 decrease the hepatic triglyceride synthesis. #ide effects 7 Myositis, nausea and impotence. %.+ 7 severe renal and hepatic dysfunction. D/ (holesterol +inding resins: 8.g 7 %holestyramine and cholestipol. M.$.2 7 2nion e0change resins. #ide effects 7 nausea and flatulence and abdominal bloating. E/ &i!otini! a!id deri*ati*es: M.$.2 7 inhibit lipid synthesis in the liver. #ide effects 7 headache, rashes, abnormal &3T. %.+ 7 pregnancy, breast6feeding.

%/ Omega # fatty a!ids: M.$.2 7 decrease the @&1& secretion. #ide effects 7 nausea and belching.

,ipid a"normality

Drug of !hoi!e #tatins 3ibrates #tatins

'ypercholesterolemia 'ypertriglyceridemia %ombined abnormalities

Target values of lipids are given the box

')Y,OIDOSIS
DE%) %linical syndromes characteri?ed by deposition of amyloid. 'myloid 7 amorphous, eosinophilic, hyaline protein deposited in between cells. Etiology: '/ %amilial: e.g familial mediterranean fever(3M3) +/ '!Juired: (2, bronchiectasis, T!, etc.

 Pathology and !lini!al features are given the bo0. Diagnosis: !iopsy of ,) (ectal biopsy -) #ubcutaneous tissue 3) "ingival 4) $rgan effected #pecific diagnosis 888 apple green birefringence with (ongo red stain under polari?ed light. )anagement: "iven the bo0. 5rognosis of generali?ed amyloidosis is bad. #urvival is about ,64 yrs. 3M3 has good prognosis.

PORPHYRI'S
DE%: (are genetic or acCuired disorders due to defective porphyrin metabolism. %haracteri?ed by cutenous and %4# manifestations with increase in urinary porphyrin precursors. )eta"olism and (lassifi!ation of porphyrias are given the bo0.

'eme synthesis mainly occurs in !one marrow ((!%) 7 for '! synthesis.

 &iver 7 for synthesis of heme proteins li e 54:;. '!ute Intermittent porphyria1'IP/ 2+5 is due to deficiency of uroporphyrinogen synthase. clinical features) %ommon in middle age. %olic y abdominal pain with no tenderness. %onstipation 5eripheral neuropathy esp. of upper limbs sei?ures 1rugs li e barbiturates, carbama?ipine etc. and alcohol can precipitate 2+5. *rine 2&2 and porphobilinogen is increased. These substances give pin colour with 8hrich/s reagent. Porphyria !utenae tarda: 1ue to deficiency of uroporphyrinogen decarbo0ylase. 5recipitating factors include alcohol. %linical features) %ommon in middle age. !ullous s in eruptions to especially in the sun e0posed areas These lesions heal with scar. *rine shows uroporphyrinogen.

5ariegate porphyria 7 has clinical features of both cutenous and 2+5.

)anagement:

'/ '!ute intermittent porphyria: 2void alcohol and precipitating drugs. 'igh carbohydrate diet to inhibit hepatic 2&2 synthesis. Morphine can be given for pain abdomen. #ei?ures can be treated with dia?epam. %orrection of fluid and electrolytes. +ntravenous hematin therapy infusion can inhibit 2&2 synthesis. !) Porphyria !utenae tarda: 2void precipitating drugs and alcohol. @enesection of -64 liters may help. %hloroCuine -:;mg -tablets per wee can reduce uroporhyrin. 2void sunlight and barrier creams can be useful.

PRE5IO$S YE'RS $&I5ERSITY K$ESTIO& P'PERS %ndocrinology can be part of medicine paper I or II
,. %linical features, lab. investigations, and management of diabetic etoacidosisS 10marks L Man 6GG@ O -. 2menorrhoea 6galactorea syndromeS@mar s OMan 6GG@O 3. &ab criteria for diagnosis of diabetes mellitusS +nvestigation and management of type - obese diabetic without complicationsS 10 marks O Mune 6GG9 4. %ushing/s syndrome causes, clinical features and investigationsS Mention long term complications of steroid therapyS 10 marks O De!6GG#4Man6GG9

:. insulin 7 discuss under following headings a) source b) purity c) indications @mar s ODe!6GG#4Man6GG9 <. 5rincipals of diet management in diabetesS10marks O Mune 6GG6 M. 8tiology and management of hypercalcemia 7 @mar sO Man6GG6 B. 1escribe briefly clinical features, diagnosis, and treatment of My0edema comaS @ mar s O Man. DAF%e" 1DDD(causes and therapy) .. 2cute complications of 1M and outline the management of 192 S@mar s OMan DA ,;. %lassify %ushing syndrome and mention clinical featuresS )ar s 6N#O Muly DA. ,,. #ymptoms of hypoglycemia and managementS )ar s 6N#O Muly DAF )ay 1DDC. ,-. %lassify hypogonadism in males and mention clinical features. )ar s 6N #. Muly DA. ,3. Mention causes of hypocalcaemia and outline the managementS )ar s #N6.Mune 6GGG, Pune-;;-, june-;;3, ,Pan ,..M, ,4. (ole of "ly 'b. Mention clinical features of hypoglycemiaS )ar s6N#. Mune6GG#. ,:. #+21'Dcauses=etiology and treatmentS )ar s6N#.De! 6GG6F )ay1DDCF Mune 6GG9 ,<. Mention four causes of hyperthyroidismS Mention clinical features and treatment of graves diseaseS Marks 2+5+3O Mune6GG1F )ay1DDCF &o* 1DDC. ,M. &ong6term complications of 1MS 2dd a note on diabetic nephropathyS )ar s6N#L Muly 1DDBF Ouly1DDDF Oune6GGGF Oune6GG6. ,B. 4: yrs obese male diagnosed to have 1M. mention minimum basic investigations reCuired and dietary adviceS Marks10O De! 6GG6. ,.. Thyroid function tests and their significanceS )ar s @ ODe! 6GG6 -;. Mention clinical features and lab investigation of 1MS )ar s@O Man 1DDBF6GG6 -,. 1efine microalbuminuriaS $ut line the management and clinical features of diabetic nephropathyS )ar s 1N6N6O Mune 6GG#1paper II/. --. 2ddison/s disease causes and management of acute adrenal insufficiencyS )ar s @O )ay1DDCF Muly1DDD. -3. $utline the clinical features and treatment of acromegalyS )ar s @O &o* 1DDC. -4. %omplications of 1M and $'2/s with dosesS )ar s 1N6N6O &o* 1DDC. -:. 1rugs of hyperlipidemiaS )ar s @O %e" 1DDD. -<. %linical features, investigations and treatment of 49'%S )ar s 6N1N6O De! 1DDD. -M. Mention various causes of polyuriaS Management of diabetes insipitusS )ar s @O De! 1DDD. -B. %auses of tetany, outline clinical features and management of tetanyS )ar s 6N6N1O De! 1DDD. -.. Mention various causes of short sutureS $utline the clinical features of acromegalyS )ar s 6N#O Muly 1DDD. 3;. %linical features of hyponatremia and managementS @mar s L Mune 6GG@ 3,. &ab diagnosis of 2ddison/s diseaseS @mar sL Mune 6GG@