Case Discussion-Dr. Raghunath

Purushothaman Kuzhikkathukandiyil Late onset seizures in 57 Year old. Reghu . please give the following details..1.Past history ,,,,,,,,,,,any illness, esp.Hypertension, diabetetis,, etc ,,,,,,any neurological problem ...... 2.Late onset seizure at this age.idiopathic epilepsy onset is unusual and more chance for organic.. .....in this case the episodes spacing does nt show an increase. but what about the other features. eg, duration of seizure , and change in pattern of seizure phenomenon ,,,,,,,,,,over these period. 3. You said apart from this seizure there is no other complaints. a little more of history details, .subtle deterioration in personality ,social relations, ...activity or hearing , vision, etc......4. In the general examination,,,,,,,,,BP , general examinatin clues any eg, skin nodules, or pigmentation or other markers....6. Any drug ( addictions also , apart from the oxcarb..........6. and the compliance of drug, and drug interference... 7 CNS exam .....fundus, etc.............

Tp Rakesh I didnt get the picture. Was there anything specific in those tests for making guess ?

Sandeep Padmanabhan DDs for GTCS in >50 yr old male with a negative imaging and EEG? Is that the question?

Sandeep Padmanabhan Alcohol Withdrawl / Metabolic are the commonest causes of GTCS at this age group. Since he had fever and loose stools 2 days prior to the ictus, possibility of alcohol withdrawl and metabolic like hypoglycemia has to be considered especially when MRI and EEG were not fruitful.Was he a diabetic on OHA or an alcoholic? Vascular risk factors? Possibility of toxin exposure?

Shiji Pv metabolic causes first as he was having fever loose stools...hyponatremia...hypoglycemia....but then how was it in previous episodes...was there fever,...

Unni Krishnan I think this may be oxcarbamazepine induced hyponatremia worsened by fluid and salt depletion due to diarrhoea. The fever is just part of the diarrhoeal illness I think. He would have had the usual 4-5 tests you would do for a low sodium - cxr, osmolality, TSH, cortisol etc...If so, main principle would be to correct slowly. Shiji and Iqbal would be able to provide an expert opinion of correction of a low sodium

Purushothaman Kuzhikkathukandiyil Yes , first possibility is metabolic in this case , (hyponatremia, , glucose either ,hypocalcemica ) Three reasons, 1. Organic cause of any sort , unlikely to remain episodic with totally normal interval , without progression, that too a six month interval between the last two .

Purushothaman Kuzhikkathukandiyil As unni pointed out , loose stool and vomiting precipitated also argue for metabolic cause .Unni , you jumped to conclusion that it is hyponatremia. ? Correction of hyponatremia..........First of all establish that it is true hyponatremia,,,,,,,,,,,ie consider other factors, esp , sugar and correct it , ie 1.6 meq for every 100 mg rise. And correction for protein or lipid in other cases

Sandeep Padmanabhan OXC can cause hyponatremia in 30%. To have Status due to hyponatremia alone and patient improving completly with Lora nd fosphenytoin is hard to believe. That is a point against metabolic alone as a cause.

Purushothaman Kuzhikkathukandiyil If true hyponatremia, the correction again depend on acute/ chronic process. especially in an older person, .........chronic hyponatremia ,lot of other compensatory factors ll be there and unless symptomatic you need not aim for a full normal correction........... Acute symptomatic hyponatremia, esp in case like this , presenting with seizures. ( discussion is deviated to hyponatremia. .......i am not culprit , Unni ..........

Unni Krishnan Agree Sandeep, I made the (possibly wrong) assumption that the drug history along with the normal brain imaging is provided to highlight the relevant past history.Usually, the chronic hyponatremia induced by drugs would not cause seizures, but I felt it may have dropped further with the diarrhoeal illness...

Purushothaman Kuzhikkathukandiyil The other factor to be considered for hyponatremia correction is the volume status , Hypo , eu , or hypervolumic hyponatremia. ..........management especilly after the initial correction depends on this.  i am just writing these as teaching notes of correction of hyponatremia. (may not be relevent for this case , ....as suggested by UNNI ) ,,,,,,,,,In symptomatic hyponatremia , of any of the above situation give saline enouth to raise to 120 meq. ie suppose sodium is 108 ..........120-108 XWeight in Kg X 0.6 meq

Sandeep Padmanabhan One of my professors observation is that,most seizures presenting to casualty are labelled GTCS. And for most Casualty doctors, Seizures = GTCS = Phenytoin. (nothing to do with this case)

Purushothaman Kuzhikkathukandiyil in hypervolemic cases you may use 3% and hypovolemic cases normal saline , to correct ,,,,,,,,,I ml of N saline contains 0.154 meq , and 1 ml of 3% saline contains 0.5 meq . of saline.........you target only 120 . the rest ie upto 135 you may correct slowly taking hours, ie 12 meq/day or 0.5 meq raise every hour. If you go fast , osmotic dismyelination likely. in all cases especillay cases like this better to have Thyroid and cortisol level

Sandeep Padmanabhan Many GTCS from casualty gets discharged from ward with a diagnosis of symptomatic localisation related seizures. Usually patients present during secondary generalisation. So to broaden the DDs one more question is to be asked. Were the seizures really GTCS?

Purushothaman Kuzhikkathukandiyil Sandeep , the overall pattern , over one year, does that argue against a focal pathology ,

Sandeep Padmanabhan But he was on OXC abeit a low dose.

Purushothaman Kuzhikkathukandiyil if it was a focal pathology one year back, in this 57years, will it remain as such for one year..........is one question ie focal pathology significant enough to cause a seizure one year back , remaining as seizure alone

Sandeep Padmanabhan Just broadening the DDs.. Focal comes lower down in the list.

Purushothaman Kuzhikkathukandiyil Sandeep your reasoning , hypo natremia if that was the reason for seizure. that would have occured much frequently at the beginnin........But as unni suggested ,another added problem of diarrohea. would have cause this, .........does that argument hold

Sandeep Padmanabhan ‎Raghu Nath has not mentioned about correction of any metabolic parameters, still the person became normal on AEDs alone, That is diffcult to explain in Hyponatremia.

Purushothaman Kuzhikkathukandiyil Reghu did nt mention the BP,,,,,,,,,,,,Fundus etc......which i feel is essential in this case

Sandeep Padmanabhan Yes. We need more details to proceed from this point.

Purushothaman Kuzhikkathukandiyil I feel we are a little biased. ...so forget about the comments on hyponatremia. , we ll hear more from Reghu. .......and we ll begin ......again ( pacha malayalathi, "" aatheem poootheem kalikkaaam "

Sandeep Padmanabhan ‎Raghu Nath.....Waiting for details of seizure semiology and brief clinical examination findings. What drugs were given other than AEDs?

Raghu Nath NOT A HYPERTENSIVE OR DIABETIC. ALL THREE EPISODES WERE GTCS.,PATIENT WAS WORKING IN A SHOP.HE HAD SOME PERSONALITY DETERIORATION ASSOCIATED.HE HAD BEEN SCOLDED BY HIS BOSS FOR MAKING SIMPLE MISTAKES.FUNDUS NORMAL.

Raghu Nath RBS 97MG,ECG WNL,S.Na-108meq/l

Raghu Nath hyponatremia initially corrected with 3% ns,followed by oral salt correction.next day it was 114,on 5th day it became 127.oxmazetol stopped and fosolin maintained.patient is not an alcoholic.no other AEDS.BP-120/90.

Raghu Nath in all previous episodes seizure was associated with loose stools,vomiting or some mild fever(according to patient).

Ramshad Ibrahim Moosa picture goes with limbic encephalites,his personality changes may b short term memory loss which is common prior to full blown picture of encephalitis plus SIADH secondary to encephalitis, limbic encephalitis will rarely produce eeg change,how s the patient now

Purushothaman Kuzhikkathukandiyil Points against Limbic encephalitis ...... , Explanation for hyponatremia ( which is well documented , worsened by loose stools and episodic ...which argues for a chronic hyponatremia worsened by superadded insults).......is difficult . Of course you may argue that limbic encephalitis is the primary neurologic problem and it leads to SIADH , OR Cerebral salt wasting...........These are more common in acute short duration cases. ..........This case presented with seizures only one year back,then definit asymptomatic period, .....episodic seizures.GTCS, responded to AED..........not much of psychiatric problems.( according to Reghu , higher function problems miner compared to seizure phenomena )......................I think it is the other way ie ,.............In a 57 year old man , Secondary Limbic encephalitis as a para neoplastic syndrome is a good possibility , but ....this duration and episodic phenomena , without much of higher function deterioration i am not convinced........

Purushothaman Kuzhikkathukandiyil Reghu,,,,,did you check Thyroid function status , and Cortisol......

Raghu Nath TSH-12miu/ml(0.3-6.2),FT3-1.8pg/ml(1.4-4.2)FT4-O.6ng/dl(.8-1.7),T4 BOUND-3.2 mig(4.3-11.9).no thyroid swelling,anti tpo-45u/ml(<60 neg).s.cortisol 8AM-4.15migram/dl(7AM TO 10 AM-6.2 TO 19.4).ACTH stimulation test not avaliable/not done.CT ABDOMEN-NLadrenals. .MRI PITUITARY-WNL.NO HYPERPIGMENTATION,THERE IS DECREASED SHAVING FREQUENCY.....OLD PTB 15 YRS BACK...sputum afb -ve.xray -fibrotic bands.plz add to this reports...

Purushothaman Kuzhikkathukandiyil Reghu , very difficult to pin point anything definit from the above values. Taking the thyroid function ,,,low values of Throid hormones. with a mild elevation of TSH .............the lesion is peripheral and pituitary is normal compensating.............Cortisol lower side in this context you have to go for peripheral ,,,,,,,ie Thyroid and adrenals both functioning low.......??????? I think better to have a repeat value ,,,,,at least TSH ....and ACTH.......

Purushothaman Kuzhikkathukandiyil What was the potasium level...........In hyponatremia , always check potasium ,,,,,,,,if you get a hyponatremia and Potasium on the higher side.........very helpful because the lesion is definitly not a central one. because mineralocorticoids is not controlled by pituitary........unlike others ..........

Prathosh Gangahar T K ‎@Raghu, Few clarifications --any autoimmune markers(like vitiligo) ?petrified ears ? volume status of the patient during admission, s K+, calcium profile,urine Na + or urine osmolarity during admission available or not ? did he receive any steroids during emergency .. Hormone profile you mentioned was done during acute stress or not ? - central hypothyroidism with secondary adrenal in sufficiency is still a possibility -- TSH can be high in central hypothyroidism( up to 20)-- usually bioinactive and immunoreactive-- due to abnl sialyation --No pigmentation.primary adrenal insufficiency is unlikely..sick euthyroid state can be tricky .. but odd to get N fT3,low fT4,and increased TSH..

Prathosh Gangahar T K Make sure that cortisol sample was taken without any steroid administration.. you can rpt T4, TSH, cortisol, with s Testosterone , LH,FSH,PRL..you mentioned features of hypogonadism.. if you put every thing together One has to consider hypopituitarism..any H/o head injury .. H/o s/o DI .. you can also inform as abt hemogram and Mg levels .. CEMRI sella you have to consider in this patient after rpt hormone profile..

Prathosh Gangahar T K few additional clinical clues also needed -- complexion(sallow or not), pubic and axillary hair status, testicular consistency , ..all suggest how long standing is the disease process..Also regarding thyroid ..

Raghu Nath s.k-3.7meq/l.s.ca-9.4mg,s.mg-2.4mg..no family history,no autoimmune markers,no volume overload,no dehydration.u.na not avaliable.no steroids during emergency.TFT and cortisol done after 5 days of admission;means under stress.repeated TFT,SAME PICTURE.patient was not willing for other hormonal assays.he had loss of libido,complexion was not normal(hypothyroid look)

Purushothaman Kuzhikkathukandiyil if we postulate a central cause.......hyponatremia must be explained as multifactorial ( drug + loose stools and the hypothyroid state ) and the adrenal hypofunction central is not contributing at all ( low cortisol due to central cause wont cause mineralo corticoid deficinecy.)...........It is a better argument because one lesion if explains everything is always nice. But ......will you get that level of hyponatremia , ........in the first situation is one question .........another is this occured one year back .......then episodically hyponatremia only..

Raghu Nath our diagnosis after consulting with our endo sir was hypopituitarism..sir also told the tsh can upto 20,we were not knowing that....

Purushothaman Kuzhikkathukandiyil Raghu can you quote referance for that .

Purushothaman Kuzhikkathukandiyil a pituitary which has lost all it reserves to stimulate thyroid is resulting in hypothyroidism..........and here we says TSH can be upto 20 during stress...........i cant agree with that view

Raghu Nath sir at that time i searched,didnt get...pradhoshettan can tell...

Unni Krishnan ‎1. For the extent/severity of hypothyroidism, the TSH response seems proportional to me. If the hormones were nearly undetectable, then you could say that the TSH rise should have been more. However, here the TSH rise seems in the range one would expect for the level of hypothyroidism, I would have thought.What do the experts think?

2. Can we go a long way with loss of libido? If he is otherwise depressed or suffering from psychological problems, would this not be enough?

3. If we say all this is central, I struggle to understand why the problems are periodic (especially over a long period with normal MRI). Also when this happened the first time why was the oxcarbamazepine not stopped? If hyponatremia happens in 30% and someone comes with convulsions and a low sodium, I would struggle to justify a reason to continue the drug.

4. Are we assuming that the fever + diarrhoea is just fever + diarrhoea? IF so, I still think the drug + diarrhoea is ample reason for the derangement. Would there be any other reason for a low cortisol? Were the levels consistently low? To my mind, the cortisol is the only unexplained finding here.

We need another pottakkannan to palpate this elephant. Iqbal, what do you think?

Raghu Nath hypothalamo-pituitary dysfuction can have even elevated tsh,explanation for this paradox is that the biological effectiveness of CIRCULATING tsh is impaired due to abnormal glycosylation secondary to reduced trh stimulation on thyrotrophs(from williams).VALUE OF 20 NOT SEEN.can hav high nl value(harrison)

Purushothaman Kuzhikkathukandiyil Reghu what was the potasium level

Purushothaman Kuzhikkathukandiyil Few points for the youngsters..........Why this arguments..........Here is a case of late onset seizures . Idiopathic epilepsy is unlikely to appear at this age.So we should always exclude organic cause. Out of this lot of focal lesions like ICSOL, Vascular,..............metabolic like sodium , calcium ,sugar disturbance........Here it is remaining stable except for episodic seizure and no focal features and not progressing. metabolic process high in the list. Here there is docuimented hyponatremia. .......too low enough to cause this seizure. That was approached in two ways. 1.Central cause for seizure and Hyponatremia secondary eg salt wasting or SIADH. 2.Hyponatremia ..as primary and seizures dut to that. No documented lesions in brain and few more points argue against first possibility ......So we take the second........Then ,what is the explanation of this hyponatremia and documented low cortisol........is it central or peripheral .......Why we ask for potasium level is , low aldosterone leads to low sodium and high potasium. If you get that it can not occur due to central cause as ,,,,,zona glomerulosa is not under controll of pituitary..............

Purushothaman Kuzhikkathukandiyil Then if you get a low sodium and normal potasium , can you explain by a central cause .........yes the dictum in hyponatremia is always rule out hypothyroidism and low cortisol state in persistant hyponatremia. The mechanism is interesting one.......The hypothalamic osmostat is reset in both these conditions, ie when the osmolarity (mainly decided by the serum sodium ) which is usually triggered to secrete ADH at about 135 ,,,,,,,is reset to a lower value , ........imagine 125.......that means each time when sodium above that level hypothalamus secretes ADH and retain water and lead to persistant low sodium state.....

Purushothaman Kuzhikkathukandiyil Here the main argument is ,,,,,,,is this the first category ie adrenal responsible fow low cortisol and low aldosterone and low sodium (high potasium) ...........or the central cause..........If it is peripheral reason , you have to find an answer for the thyroid status........If potasium is normal , it is better to explain by a central mechanism......There again the problem is you got a rather high TSH............So in order to solve these issues..........we need two things ,,,,,,,,1.Level of potasium 2. Repeat TSH .

Prathosh Gangahar T K ‎@Purushu sir,high TSH is a paradox . ref Williams P322, explanation is high TSH measured by immunoassay is not biologically activel because it is abnormally glycosylated..We are also seeing such cases here..TSH can be 1-20 (table 10-12) with ft4 low ft3 N or low..Other explanation for low cortisol and high TSH is primary adrenal insufficinency(TSH-5-30) but Ft4 n Ft3 n or low..i will not consider primary here pigmentation is absent..thyroid profile not suggestive..

Prathosh Gangahar T K ‎+ Raghu mentioned K 3.7, rpt TFT same picture.. Hyponatremia is definitely multifactorial --hypothyroidism.. secondary adrenal insufficiency+ depletional + OxCBZ..

Suneesh Kalliath We had a female patient admitted with hyponatremicseizures ,had hypothyroidism..

Prathosh Gangahar T K ‎@Unni.. Raghu mentioned reduced shaving frequency not decreased libido we hav to assume it as hypogonadism unless proven otherwise..although it needs confirmation with other clinical as well as hormonal profile.. Central causes metabolic derangement can be periodical ..depending on any acute stress like fever .

Prathosh Gangahar T K Other points need to be asked -- H/o snake bite, goiter status..

Prathosh Gangahar T K Raghu how did you manage this patient?.. what is the metabolic abnormality you expect on initating Rx? MRI brain are you able to visualise sella ?

Prathosh Gangahar T K Finally you can explain high TSH with primary subclinical hypothyroidism( especially if TPO is positive) in present scenario .. ie with coexisting lymphocytic hypophysitis in PolyGlandular Autoimmune syndrome..

Unni Krishnan So in order to reduce the possibility of this happening again, what do we do?

My list would now include:
1. STOP Ox Carb
2. Start L thyroxine (100 mcg perhaps?)
3. ? Fluodrocortisone (maybe OD 100 mcg OD)
4. Investigate into the cause of the febrile diarrhoeal illness - is this just recurrent viral gastroenteritis?
5. Re-image the sella in 12/12?

Please revise the list as appropriate. Thanks.

Purushothaman Kuzhikkathukandiyil Unni, no need for fludrocortisone supplementation here. Just stoping oxcarb. supplementing thyroxine and cortisol ll do.......that itself ll reverse the sodium.....in this case potasium normal argues that it is not mineralo corticoid deficiency.......

Unni Krishnan Would you reimage the sella? And what is the working endocrine diagnosis here?

Purushothaman Kuzhikkathukandiyil Unni, now with the normal value of potasium and Explanation for TSH value , it is better to go for pituitary where you may get a normal MRI. i am not convinced about the autoimmune hypophisitis part.( may be i dont have much experience to comment on that )... i ll be happy with this investigations provided he is better. No plan for re imaging. But i ll follow up the electrolytes closely ( which is cheap and must .........

Prathosh Gangahar T K basic diagnosis is Hypopituitarism needs evaluation for aetiology..needs replacement with hydrocortisone followed by LT4.. start with a low dose of T4 (exclude underlying cardiac disease)..direct initiation of LT4 will precipitate adrenal insufficiency hence should be stared with hydrocortisone cover..Fludro is not needed unless is a long standing severe secondary adrenal insufficiency with B/L adrenocortical atrophy ie in practice very rare ..work up for febrile illness if fever spikes.. treat hypogonadism with parenteral testosterone.. watch for unmasking of DI..

Prathosh Gangahar T K Re imaging is needed ideally, usual MRI brain sellar cut may not be good ..partial empty sella , stalk thickening is usually missed..any of these findings need further work up.. for eg :in view of past h/o PT one has to consider granulomatous hypophysitis..

Purushothaman Kuzhikkathukandiyil Prathosh , in autoimmune or granulomatous hypophysitis. .....the deficnecy of hormones devolop sequentially or simultaneous. ..?

Purushothaman Kuzhikkathukandiyil For the youngsters. Please not a very important practical point Pointed out by prathosh ..........In hypothyroidism of central origin.......never be in a haste to start Thyroxin............correct the cortisol .........then only start thyroxin.........

Prathosh Gangahar T K ‎@ Purushu sir,Recently we came across a patient with hyponatremia..on evaluation had anemia with features of sub acute combined degeneration petrified ossicles..with low ACTH, cortisol, LH , FSH, T, FT4 , high PRL(64), TSH(36),TPO strongly positive,low IGF 1 MRI brain N CEMRI sella partial empty sella,negative celiac work up.. He developed manifest DI during replacement.. also PCA ab was neg..Diagnosis we kept was PGA - Hypopituitarism - likely autoimmune hypophysitis+ autoimmune primary hypothyroidism+ pernicious anemia with subacute combined degeneration.so rarely one can come across with a combination of primary and secondary hypothyroidism..

Prathosh Gangahar T K ‎@Purushu sir, AH- Usually hormone deficiency occurs acutely ACTH def. more common (57%) followed by T4, LH,FSH,GH, PRL.. it is not sequential unlike a mass lesion.. But hypothyroidism can manifest late (after 9 months )..Granulomatous H- one has to suspect in a clinical scenario with hypopituitarism and DI..

Purushothaman Kuzhikkathukandiyil One doubt prajosh......in a case before clinical investigations, ..where you are not sure whether it is central or peripheral hypofunction,,,,,,loss of sexual hair ..will it argue more for pituitary ..........

Prathosh Gangahar T K features of hypogonadism definitely a clue for central cause especially associated with other hormone deficiencies...But loss of sexual hair can be seen in primary adrenal insufficiency in females( DHEAS is the predominant androgen-absent in AC insufficiency )