grand roufn about std

1. GRAND ROUND
HYPOTHYROIDISM
Moderator: Samir Abdi M.D (Internist)
Presenter: Abdirisak Jacda M.D (R1 IM)
8/18/2023

2. Summary
 Hx 20 yrs. old woman with known history of recurrent ascites
 CC.. Worsened body swelling last 2 months
 HPI she was having recurrent ascites body swelling for last 2 years but
worsened last two 2months the swelling spread from abdomen to
extremities then lastly to her face,
 ROS
 respiratory SOB orthopnea Cough
 Neuro headache dizziness and
 Cardiac palpitation anasarca
 GU freq, urgency, burning, dysuria with flank pain
 GI epigastric pain nausea constipation
 General fatigue loss of appetite but no fever or night sweet

3. Summary
 Past obhx two previous NSVD with later one with PPH
 Pmhx two paracentesis one therapeutic and one diagnostic
 Fmhx no similar case
 Social hx:- near baki district
 Drug hx frusemide 40mg od po Paracetamol 500mg po PRN

4. Phsyicals
 Vitals BP 120/75 P. 117 O2 stat 96% T 36.5 RR 26
 Day 2 vitals
 BP 140/90 P. 96 O2stat 88% T 37.4 RR 22
RBG 207 FBS 124
 Generally, young aged woman looking sick with profound
anasarca
 HEENT, severe pallor on congictiva nails and palms
 neck, painless diffuse goiter mobile with swallowing

5.  Cardiac:- unremarkable
 Lungs:- orthopnea in day one bilateral basilar crackles with
dullnes on percussion
 Abdomen non-tender, distended due to gravidarum. Have also
shifting dullnes with active bowel sounds
 Neuro GCS of 15/15
 Periphery bilateral biting edema

6. Date Before admission Day 1 on admission Day 6 on admission
HGB 8.6 7.7 9.1
MCV 89 86 87
PLT 361 Normal Normal doen to rule out
preecalpsia
Cr 1.2 0.8 0.6
BUN 49 38 32
UA
WBC
LE
Protein
Serum
albumi
n
Numerous
+++
++++
20g/L or 2mg/dL
TSH 0.54 Recheck 0.48
T3 0.5
T4 37.5
HbsAg Positive

7. Blood grouping and cross match done
Revealing
ORH-ve

10. X-ray
 Bilateral lower lobe small pleural effusion.

11. What is your DDX

12. Assessments
1. UTI
2. Hypothyroidism
3. AKI
4. Nephrotic syndrome
5. Chronic HBV infection
PLAN
• Two Units of blood given
superheema 1 ampule BID
• Augmentin 625mg BID
• Tramadol 50mg IM PRN
• Omeprazole 20mg po od
• Levothyroxine 100mg po od
• Dexamethasone 6mg IM BID

13. Ddx ?????
1. Nephrotic syndrome
2. Preeclampsia
3. Hypothyroidism

14. For nephrotic syndrome
 Protein loss from kidney
 3-4 gram per dipstick
 Anasarca
 Hypoalbuminemia
Against
Hypothyroid sx

15. NEPHROTIC GNs
 less inflammation (proliferation) than the nephritic GNs
 “nephrotic” urine:
 see less hematuria, more proteinuria
 azotemia less common, or at least less rapid
 hypertension not as common

16. NEPHROTIC SYNDROME
Is a syndrome, not a disease
 collection of symptoms and signs due to a common pathology
Can be caused by a variety of diseases
Must look for the specific disease

17. DEFINITION
Syndrome consisting of the following:
 proteinuria > 3.5 grams/24 hrs
 hypoalbuminemia
 hyperlipidemia and lipiduria
 peripheral edema

18. MECHANISM
glomerular abnormality  “nephrotic” range
proteinuria is initial insult
 generally > 3.5 grams/24 hrs
hypoalbuminemia

19. HYPOALBUMINEMIA
 due to  losses in urine
 liver attempts to compensate by  albumin synthesis (up to 50-
60%)
probably in response to  plasma oncotic pressure
 general correlation between urine losses and serum levels

20. MECHANISM
glomerular abnormality  “nephrotic” range
proteinuria is initial insult
 generally > 3.5 grams/24 hrs
hypoalbuminemia
hyperlipidemia/lipiduria

21. HYPERLIPIDEMIA
 see  triglycerides, VLDL, LDL, Lp(a) in serum
 see  lipid in urine in form of:
free fat droplets
fatty casts
oval fat bodies

23. HYPERLIPIDEMIA
 vascular risk likely the same as for non-
nephrotics
 nephrotic pts may have 5.5x greater risk for MI
 HMG CoA reductase inhibitors (“statins”)
are drugs of choice

24. MECHANISM
glomerular abnormality  “nephrotic” range
proteinuria is initial insult
generally > 3.5 grams/24 hrs
hyperlipidemia/lipiduria
hypoalbuminemia
peripheral edema
(+ renal salt retention)

25.  Glomerulopathy
 Primary
 Secondary
 some glomerulopathy
 can present as more than one syndrome at different times

26. The Spectrum of Glomerular
Pathology
The Nephritic-Nephrotic Spectrum
 a clinical picture anywhere on a spectrum with
pure nephritic and pure nephrotic syndromes
at the extremes

27. Glomerular Disease:
Pathogenesis
 Genetic mutations
 Infection
 Toxin exposure
 Autoimmunity
 Atherosclerosis
 Hypertension
 Emboli
 Thrombosis
 Diabetes mellitus

28. Spectrum of glomerular diseases

29. EDEMA
HEART LIVER KIDNEY CAP LEAK
urinalysis
nephrotic nephritic
MCD
MGN
FSGS
DMN
IgAN
IgAN
SLE
antiGBM
IC
ANCA
(quantitate proteinuria)
LYMPH/VEINS

30. OTHER COMPLICATIONS
 progression to ESRF
 EDEMA
 infection
 hypercoagulation
 risk of complication correlates with degree of proteinuria
 reduction of proteinuria leads to reduction in risk
 if proteinuria cannot be reduced, then risk must be addressed
hyperlipidemia

31. NEPHROTIC SYNDROME
Minimal Change
Disease Membranous
Glomerulonephropathy
Focal Segmental
Glomerulosclerosis
Diabetic Nephropathy Amyloidosis

32. NAMES
Minimal Change Disease
Membranous GN
FSGS

33. EPIDEMIOLOGY
Minimal Change Disease = kids
FSGS = everyone
Membranous = adults
0 yrs 65 yrs
100%
0%

34. PATHOGENESIS
MCD and FSGS
 T cells produce abnormal cytokine that leads to
glomerular epithelial cell damage
 retraction of podocytes due to ?interaction with anchoring
proteins
 b-dystroglycan
 a3-b1 integrin
Membranous
 due to immune complex deposition

35. PATHOGENESIS
Causes
 most commonly idiopathic (“primary”)
 90% of cases
 may be secondary to:
 drugs..(NSAIDs, lithium, gold)
 malignancy
 infections..(HIV, hepatitis B+C)

36. PRESENTATION
Symptoms
 usually present with
edema
 facial, lower limb,
arms/hands
 often quite abrupt
with MCD
 otherwise well. .don’t look
sick
 may complain of foamy
Signs
 pitting edema in
dependent areas
 usually not much else

37. INVESTIGATIONS
Urine
 dipstick strongly (+) for protein, little
blood
 usually more than 3.0g/24 hr on
collection
 microscopy shows lipiduria
 free fat droplets
 oval fat bodies
 fatty casts
Blood
 hypoalbuminemia
 hyperlipidemia
 creatinine usually normal or mildly
elevated

39. DIAGNOSIS
 cannot differentiate between various nephrotic
GNs from history/exam alone
 firm diagnosis depends on renal biopsy

40. PROGNOSIS
MCD MGN FSGS
Persistent
proteinuria
60-70% remit or
stabilize
persistent
proteinuria
Renal failure
usually NOT a
concern
30% chance of
progression to ESRF
over 15 yrs
5 yr renal
survival 60-90%
10 yr renal
survival 30-50%

41. TREATMENT
MCD
 corticosteroids the drug of choice
 in children, biopsy usually not done straight to steroids with nephrotic
syndrome
 in adults, biopsy usually done for diagnosis first
 1 mg/kg daily usual dose
 may require 4-8 wks. before response is seen

42. TREATMENT
MGN
 all pts should receive angiotensin converting
enzyme inhibitors (ACEi) or angiotensin receptor
blocking agents (ARBs)
 2nd line treatment reserved for those pts at risk of
progression
 elevated creatinine at presentation
 normal GFR after 3 yrs is good sign
 proteinuria > 10g/24 hrs
 esp if > 6 months duration

43. TREATMENT
FSGS
 corticosteroids the drug of choice
 2 mg/kg alternate days is usual dose
 may require 3 months before response is seen (often 6-9 months for full
response)
 50% remission rate

44. TREATMENT
3 main 2nd line agents include
 corticosteroids
 variable results when used alone
 best used in combination with another agent
 cyclophosphamide
 probably more effective than steroids alone but
higher toxicity
 cyclosporine
 may also be useful as first line…usually less toxicity

45. MGN and FSGS
Recommendations
 asymptomatic, protein < 3.5 g/day  ACEi/ARB
 asymptomatic, protein > 3.5 g/day and no risk factors 
ACEi/ARB
 symptomatic, protein > 3.5 g/day  ACEi/ARB + 2nd line
agent
 asymptomatic, protein > 3.5 g/day + risk factors 
ACEi/ARB + 2nd line agent

46. TREATMENT
MCD MGN FSGS
corticosteroids
(prednisone)  30% 
2ND line agents rarely 30% 50%
plasmapheresis 10%
(post
transplant)

47. TAKE HOME MESSAGE
 some glomerular diseases present with a
“nephrotic” picture
 proteinuria, edema, hyperlipidemia,
hypoalbuminemia
 thrombosis, infection
 these diseases may progress to ESRF but
usually very slowly
 renal Bx is usually the only way to make a
firm diagnosis

48. Hypothyroidism

49. For hypothyroidism
 Sx
 edema constipation fatigue
 Signs
 loss of outer 1/3 of eyebrows
 Congestion abdominal
distension shifting dullnes,
bibasilar carckles bitting
edema till knees
 Labs low T3/T4 and low TSH
Against
 Labs
 proteinuria
 Hypoalbuminemia

50. Classification of Hypothyroidism
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A. Primary
1. Enlarged Thyroid
- Hashimoto’s (65%)
- Iodine Deficiency
(25%)
- Drug-induced
(Lithium)
- Dysharmonogenesis
2. Normal Thyroid
- Spontaneous Atrophic
Primary contd..
3. Post Ablative
- Permanent
- Transient
- Sub-clinical
4. Congenital
B. Secondary / Central
Pituitary/ hypothalamic

51. IDD
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52. Clinical considerations
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Disease Burden
1. 5% of the general population are Sub-clinically Hypothyroid
2. 15 % of all women > 65 yrs. are hypothyroid
3. Detecting sub-clinical hypothyroidism in pregnancy is highly essential
– order for TSH and FT4 routinely in all pregnant women at the
beginning of each trimester
4. All persons aged above 60 years – Order for TSH

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Multi system effects - Hypothyroidism
General
•Lethargy, Somnalence
•Weight gain, Goitre
•Cold Intolerence
Cardiovascular
•Bradycardia, Angina
•CHF, Pericardial Effusion
•HyperlipIdemia,
Xanthelsma
Haematological
Iron def. Anaemia,
Normo cytic /chromic
Anaemia
Reproductive system
•Infertility, Menorrhagia
•Impotence, Inc. Prolactin
Neuromuscular
•Aches and pains
•Muscle stiffness
•Carpel tunnel syndrome
•Deafness, Hoarseness
•Cerebellar ataxia
•Delayed DTR, Myotonia
•Depression, Psychosis
Gastro-intestinal
•Constipation, Ileus,
Ascites
Dermatological
•Dry flaky skin and hair
•Myxoedema, Malar
flushes
•Vitiligo, Carotenimia,

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Clinical Signs of Hypothyroidism
 Coarse Hair; Dry cool and pale skin
 Goitre (not in all cases), Hoarseness of voice
 Non-pitting oedema (myxoedema)
 Puffiness of eyes and face
 Delayed relaxation of DTR
 Slow hoarse speech and slow movements
 Thinning of lateral 1/3 of eye brows
 Bradycardia, pericardial effusion

56. What the mind knows the eyes see !!
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 Psychiatric patients
 Elderly women / men
 Patients of OSA
 Hypercholesterolemia
 Lithium, Amiodarone
 Postpartum women
 Other Autoimmune disease
 Rx. Grave’s Ophthalmopathy
 Family H/o thyroid disease
 Neck irradiation therapy
 Previous Rx for thyrotoxicosis
 Autoimmune Thyroiditis
Order for TSH alone as a screen

57. Clinical Photographs
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58. Congenital Hypothyroidism
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61. Endemic Goiter
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Urine Iodine Conc. < 50 µg/L

63. Myxedema
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64. Myxedema
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65. Macroglossia
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Massive Pericardial Effusion in Hypo
20.2.98

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Clearing of Pericardial Effusion with Rx.
26.7.98

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Reappearance of Pericardial Effusion
after treatment is discontinued
14.9.99

69. Hormone replacement
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70. Many Causes, One Treatment
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 Normalize TSH level regardless of cause of hypothyroidism
 Once daily dosing with Levothyroxine sodium (1.6µg/kg/day) this
comes to 100 mcg per day
 Monitor TSH level at 6 to 8 weeks, after initiation of therapy or
dosage change

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• Treatment of choice is levothyroxin
• Branded thyroxine recommended
• No divided doses - illogical
• Not recommended for use :
 Desiccated thyroid extract
 Combination of thyroid hormones
 T3 replacement except in Myxedema coma
Many Causes, One Treatment

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 Age (in elderly start with half dose)
 Severity and duration of hypothyroidism (↑ dose)
 Weight (0.5µg/kg/day ↑ upto 3.0µg/kg/day)
 Malabsorption (requires ↑ dose)
 Concomitant drug therapy (only on empty stomach)
 Pregnancy ( 25% ↑ in dose), safe in lactating mother
 Presence of cardiac disease (start alternate day Rx)
Dosage Adjustments

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 Goal : normalize TSH level – 25, 50 and 100 mcg tablets avail.
 Starting dose for healthy patients < 50 years at 1.0 µg/kg/day
 Starting dose for healthy patients > 50 years should be < 50 µg/day. Dose ↑
by 25 µg, if needed, at 6 to 8 weeks intervals.
 Starting dose for patients with heart disease should be 12.5 to 25 µg/day and
increase by 12.5 to 25 µg/day, if needed, at 6 to 8 weeks intervals
Start Low and Go Slow

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How the patient improves
 Feels better in 2 – 3 weeks
 Reduction in weight is the first improvement
???????????????????
 Facial puffiness then starts coming down
 Skin changes, hair changes take long time to regress
 TSH starts showing decrements from the high values
 TSH returns to normal eventually

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The Commandments

76. 76
The Commandments
 Highly suspect
hypothyroidism
 Growth and pubertal delay
 Unexplained depression
 TSH is the test in Hypothy.
 TSH, FT4 to confirm Dx.
 Nine square magic
 Test cord blood for TSH
 All obese patients TSH a must
 For all pregnant -test TSH,
FT4
 Postmenopausal 15%
Hypothy
 Start low and go slow
 Use Levothyroxine only
 Always on empty stomach
 Thyroxine - avoid empirical
use

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• Case Report
• A 60years old male patient presented with symptoms of
insidious onset, painless, progressive abdominal
distension since 2 months and progressive swelling of
both lower limbs since 1 month.
• He also had constipation and progressive hoarseness
of voice for 2 months.
• He had no history of chest pain, shortness of breath,
orthopnea, paroxysmal nocturnal dyspnea, jaundice,
abdominal pain, hematemesis, melena, urinary symptoms,
anorexia or weight loss.
• He was a chronic smoker for last 25 years and non-
alcoholic.

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• Examination revealed mild periorbital and facial puffiness along
with bilateral pitting pedal edema.
• His skin was dry and coarse.
• Neurological examination revealed delayed relaxation of ankle
jerks.
• The patient was afebrile with a pulse rate of 75/min, blood pressure
130/80 mm of Hg and elevated jugular venous pressure.
• On cardiopulmonary examination there was muffled heart sounds
with absent breath sounds.
• Chest radiograph showed massive cardiomegaly with bilateral
pleural effusion.
• Ultrasonography abdomen showed moderate ascites and computed
tomography chest and abdomen revealed massive pericardial
effusion, bilateral pleural effusion and moderate ascites.

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• Electrocardiogram showed low voltage QRS complexes .
• 2D Echocardiogram done subsequently showed a large
circumferential echo free space consistent with massive pericardial
effusion and evidence of cardiac tamponade (diastolic collapse of
right atrium and right ventricle free wall) with preserved left
ventricular systolic function, ejection fraction 55%.
• Viral serology for both hepatitis B and C were negative,
• UGI endoscopy and colour doppler of abdomen were done to
rule out portal hypertension and both were normal.

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 Ascitic fluid study showed total cells of 100/ cumm with 98%
lymphocytes, high protein (3.24 gm%) and high serum ascitic
albumin gradient (SAAG - 1.91) and normal adenosine
deaminase level (ADA - 6.8 U/L) .
 Pleural fluid examination showed total cells of 200 / cumm
with 90% lymphocytes, high protein (3 . 97 gm%), normal
sugar and normal ADA level (8.1 U/L).
 Cytology of both the fluids were negative for malignancy.
 In view of cardiac tamponade, pericardiocentesis was done with
aspiration of about 1500 ml straw colour fluid.
 Analysis of fluid showed total cells of 10 /cumm with high protein
(5.3 gm%), normal ADA level (8.3 U/L), and cytology revealed
mainly lymphoid and degenerated cells but no malignant
cells.
 Culture of the pericardial fluid was negative for bacteria and acid

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 Thyroid function tests showed TSH 137.8 mIU/ml (normal
range 0.4 – 4), free T4 0.45 ng/dl (normal range 0.89
 – 1.76), and free T3 0.63 pg/ml (normal range 0.92 – 2.78).
 Ultrasonography revealed atrophic changes in both thyroid
lobes. TPO antibody was negative.
 Subsequent hospital course was uncomplicated and he was
discharged with gradually escalating dose of levothyroxine
from 50 to 100 microgram daily.
 On 4 weeks follow up he was in good health and had
abatement of ascites, pleural effusion and tissue edema
and only minimal pericardial effusion left.
 His TSH was 30.1m IU/ ml and he continued on a
maintenance dose of 100 microgram with regular follow up.

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 The recent studies, however, conclude that PE is extremely
infrequent in hypothyroidism, with an incidence of 3% to 6%.
 The mainstay of treatment for thyroid PE is simple thyroxine
replacement, except in those patients w i t h pericardial
tamponade or impending tamponade, this condition mandates
urgent pericardiocentesis.
 Pleural effusion per se due to hypothyroidism is rare and
requires careful exclusion of other associated conditions.
 Effusions solely due to hypothyroidism have borderline
characteristics between exudates and transudates and show
little evidence of inflammation.

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 In conclusion hypothyroidism can have rare modes of
presentations
 .
 It can present with either isolated effusion or in
combination of multiple body cavity effusions along with
tissue edema.
 High index of clinical suspicion is required to diagnose
such cases.
 The treatment is simple and gratifying with almost
complete regression of findings after thyroid hormone

84. pre-eclampsia
 Summary brief summary
 And ddx with treatment and referral to obstetrician of maternity
ward

85. For pre-eclampsia
 Proteinuria
 Generalized edema
 Hypo-albuminemia
Against
Goiter
Normotensive
Normal liver enzymes
Normal platelet count