Kuliah semester 4

Diabetes Mellitus Tipe 1

Kongenital Hipotiroid
DR. dr. Harjoedi Adji Tjahjono, SpA(K)

Child Helath Department

Faculty of Medicine Brawijaya University
Saiful Anwar Hospital
2021

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1. Growth:
1. Short stature:
1. FSS (Familial Short Stature)
2. CDGP Constitutional Delay Growth & Puberty)
3. GH deficiency
4. Syndrome: Turner, Prader Willy, Noonan, etc
2. Tall stature:
1. Marfan syndrome, Klinefelter syndrome
2. Puberty:
1. CD Puberty
2. Precoious puberty
3. Delayed puberty
4. Gynecomastia, Premature telarche, Premature adrenarche
3. Diabetes:
1. Type 1 DM
2. Type 2 DM
3. DKA (Diabetes Keto Acidosis), hypoglicemia, Obesity
4. Hypothalamus – pituitary: brain tumor
5. Thyroid:
1. Congenital Hypothyroid
2. Hyperthyroid: hashimoto, grave
3. Hypoparathyroid
6. Adrenal:
1. Adrenal disorders: CA hyperplasia, CA hypoplasia
7. Disorders sexual development (sex ambiguity, micropenis, undescended testes
8. Metabolic: def. vit D Rickets, osteoporosis, osteogenesis imperfecta, etc
9. Syndromology: Danish drash syndr., cushing syndr, 2etc
Gary Hall Jr.

Olympic
swimming
medalist

Type 1 diabetes
Nicole
Johnson
Miss America 1999
Type 1 diabetes
Banting and
Best
1923 Nobel Prize for
discovery and use of
insulin in the
treatment of IDDM
 Differential Diagnosis of Type 1
and Type 2 Diabetes
Type 1 Diabetes Type 2 Diabetes
Usual clinical course Insulin-dependent Initially non-insulin-dependent
Usual age of onset <20 years (but ~50% over 20 >40 years but
years) increasingly earlier
Body weight Often lean but ~50% Usually obese
overweight or obese
Onset Often acute Subtle, slow
Ketosis prone Yes No
Family history ≤15% with 1st-degree relative Common
Frequency of HLA-DR3, DR4, Increased Not increased
DQB1*0201, *0302
Islet autoantibodies Present Absent
(GADA, ICA, IA-2A, IAA,
ZNT8A)

GADA, glutamic acid decarboxylase; HLA, human leukocyte antigen; IAA, autoantibodies to insulin; IA-2A, tyrosine phosphatase insulinoma
antigen; ZnT8A, zinc transporter 8.
*Needs to be refined for nonwhite population groups.
Rewers M. Diabetes Metab J. 2012;36:90-97. 6
 Classifying Diabetes
High-risk HLA* Autoantibody negative
DR3/4, IAA+ at onset
DQ1B1*0302, GADA+
DR4/4, DR4/8, IA-2A+ C-peptide (ng/mL)
DR3/3 or
(10% of T1D ZnT8A+
population) <1.0 ≥1.0

HLA+ T1aD = 80%

T1bD T2D
HLA-
5% 10%

GADA, glutamic acid decarboxylase; HLA, human leukocyte antigen; IAA, autoantibodies to insulin; IA-2A, the tyrosine phosphatase insulinoma
antigen; ZnT8A, zinc transporter 8; T1aD, type 1 (immune-mediated) diabetes; T1bD, type 1 (idiopathic) diabetes; T2D, type 2 diabetes.
*Needs to be refined for nonwhite population groups.
Rewers M. Diabetes Metab J. 2012;36:90-97. 7
 Etiologic Classification of
Diabetes
Insulin deficient Insulin
deficient/resistant

Immune Nonimmune Monogenic Polygenic

mediated mediated

Type 1a Type 1b MODY PNDM Type 2

Typical (HLA-DR3, 4, or 9) Fulminant HNF4A KCNJ11
Slow progressing Idiopathic GCKABCC8
LADA HNF1A, 1B INS
APS1, IPEX PDX1 PTF1A
NeuroD1 EIF2AK3
~5% – 20% of
all DM
APS1, autoimmune polyendocrine syndromes 1; HLA, human leukocyte antigen; IPEX, immunodeficiency, polyendocrinopathy,
enteropathy, X-linked syndrome; LADA, latent autoimmune diabetes of adults; MODY, maturity-onset diabetes of the young; PNDM,
permanent neonatal diabetes mellitus.
Rewers M. Diabetes Metab J. 2012;36:90-97. 8
 Diagnostic Criteria
• Symptoms of diabetes and a casual
plasma glucose ≥200 mg/dl, OR
• Fasting plasma glucose ≥126 mg/dl, OR
• 2-hour plasma glucose ≥200 mg/dl during
an oral glucose tolerance test.
• In the absence of unequivocal
hyperglycemia, these criteria should be
confirmed by repeat testing on a different
day.
 Presenting Signs/Symptoms

• Polyuria, Polydipsia
• Nocternal enuresis
• Polyphagia
• Weight loss
• Fatigue, weakness
• Blurry vision
• Ketoacidosis: abdominal pain, nausea,
vomiting, mental status changes
 Epidemiology

• Prevalence 1:300
• Peak age of diagnosis: 11-13 y/o
• Risk for sibling: 6%
• Risk for monozygotic twin: 50%
• Risk for offspring: 2-10%, higher side if
father has diabetes
• Highest incidence: Finland, Sardinia
 Pathophysiology
• Autoimmune destruction of pancreatic
β-cell
• Antibodies:
– Islet cell
– Insulin
– Anti-glutamic acid decarboxylase 65
• T-cell mediated
• Lymphocytic infiltration
 Pathophysiology

• Genetic susceptibility
– Association with HLA DR3/4, DQ 2/8 alleles
• Environmental triggers
– Viruses: congenital rubella, coxsackievirus,
enterovirus, mumps
– Early exposure to cow’s milk
– Endocrine chemical disrupter
 Progression to Type 1 DM
Autoimmune
markers
(ICA, IAA, GAD)
Autoimmune
destruction
Islet
Cell Honeymoo
Mas n
s

“Diabetes 100% Islet

threshold” loss
 Associated Autoimmune
Disorders
• Thyroid (Hashimoto’s, Graves’): 5-10%
• Celiac Disease: 6%
• Addison’s disease: <1%
 Management

1. Insulin
2. Diet
3. Exercise
4. Education
5. Blood Glucose Monitor
 The Miracle of Insulin

Patient J.L., December 15, 1922 February 15,

1923
c. 1923
 Insulin Preparations - US

• Novo Nordisk • Lilly

– NovoLog (aspart) – Humalog (lispro)
– NovoLog Mix 70/30 – Humalog Mix 75/25
– Novolin® R – Humulin® R
– Novolin® N – Humulin® N
– Novolin® 70/30 – Humulin® 70/30
• Sanofi-Aventis – Humulin® 50/50
– Lantus® (glargine) • Lente, Ultralente
have been
discontinued
 Treatment with Insulin

• Total daily requirement:

– 0.5-1 unit/kg/day
– 1.5 units/kg/day during puberty
• Typical Regimens
– NPH and Regular
– Basal/Bolus: glargine and Novolog/Humalog
 Insulin Delivery

• Vials and syringes

• Pens
• Insulin pump
 Physiological Serum Insulin
Secretion Profile
75
Breakfast Lunch Dinner
Plasma insulin (µU/ml)

50

Dawn
phenomenon
25

4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Time
 NPH and Regular
75
Breakfast Lunch Dinner
Plasma insulin (µU/ml)

50
R R

N N
25

4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Time
 NPH and Regular

2/3 NPH
AM 2/3
1/3 Regular

½ NPH (2/3)
PM 1/3
½ Regular (1/3)
 NPH and Regular

• Regular insulin given 30 min prior to a

meal
• NPH dose often given at bedtime
• Prescribed amount of carbs at
meals/snacks
 NPH and Regular

• AM blood glucoses → Evening NPH

• Lunch → AM Regular
• Dinner → AM NPH
• Bedtime → PM Regular
 Basal/Bolus
Breakfa Lunc Dinne
st h r
Aspart Aspart
o
Aspart o o
Lispro
r Lispro
r r
Plasma

Lispro
insulin

Glargine

4:0 8:0 12:0 16:0 20:00 24:0 4:0 8:0

0 0 0 0 Tim 0 0 0
e
 Basal/Bolus
• Basal: glargine, 50% total daily dose
• Bolus: NovoLog or Humalog
– Insulin to carbohydrate ratio
– Correction

BG – target
Correction
factor
 Basal/Bolus

• I:CHO = 450/total daily insulin dose =

amount of carbs 1 units will cover
• Correction Factor: “1700 rule” = 1700/TDD
• Glargine can not be mixed with any other
insulins
 Basal/Bolus

• Glargine dose limited by which blood

sugar?
– 2 AM and breakfast
• Which blood sugar is affected by the
I:CHO ratio?
– 2 hour post-prandial
 NPH and Regular

• Advantages
– 2-3 shots per day
– “Easier” – less carb counting and calculations
• Disadvantages
– Strict dietary plan
– Less flexible
– Less physiologic
 Basal/Bolus

• Advantages
– More physiologic
– More flexible
– Less hypoglycemia
• Disadvantages
– More labor-intensive (CHO counting, insulin
calculations)
– At least 4 injections per day
 Diet

• Healthy, balanced diet

– 50-60% total calories from carbohydrate
– <30% fat
– 10-20% protein
• Carbohydrate counting
• No forbidden foods - moderation
• Eating too much will not cause ketosis
 Exercise

• Increases sensitivity to insulin

• Helps control blood sugar
• Lowers cardiovascular risk
• Blood sugar usually decreases but may
initially increase
• Hypoglycemia may occur during,
immediately after, or 8-24 hours later
 Exercise

• Check blood sugar before, during, after

• Always have snacks available
• May need extra snacks or decreased
insulin (learn from experience)
– Usually 15 gm CHO for every 30 min vigorous
exercise
• Do not exercise if ketones are present
 Psychosocial Support

• Every newly diagnosed family should meet

with a psychologist
• Guilt
• Anger
• Fear
• Denial
• Depression
 Honeymoon Phase

• Educate that it may happen

• Diabetes is not cured!
• Occurs within first 3 months of diagnosis
• Insulin requirements <0.5 units/kg/day
• Lasts weeks to up to 2 years
• Resolution of glucotoxicity, recovery of
residual β-cell function
 Long Term Complications

• Retinopathy
• Nephropathy
• Neuropathy
• Cardiovascular disease

• Prevention by optimal glucose control

 Diabetes Control and
Complications Trial
Conventional Therapy Intensive Therapy
• 1-2 injections/day • ≥3 injections/day
• Mean A1c 9% • Mean A1c 7%

• 1983-1993, early termination given results

• Intensive therapy delays onset and
progression of long-term complications in
type 1 diabetes
 Diabetes Control and
Complications Trial
• Intensive therapy reduced risk by:
– 76% for retinopathy
– 54% for nephropathy
– 69% for neuropathy
– 41% for macrovascular disease
• Adverse events
– Hypoglycemia
– Weight gain
Prayer Sign
Limited joint
mobility
Associated with:
poor control,
increased risk of
retinopathy,
nephropathy
 Monitoring

• Hemoglobin A1c – every 3 months

• Celiac screen – at diagnosis and if ssx
• Annually
– TSH
– Ophthalmology exam - after 10 and 3-5 yrs
disease
– Urine microalbumin - after 10 and 5 yrs disease
– Lipid panel - puberty, unless fam hx, q5 years if
normal
– Influenza vaccine
 Hemoglobin A1c
A1C BG

• Reflects blood 6 135

glucose over the 7 170
past 3 months
• Goal <7 for adults 8 205
<7.5% for teens 9 240
<8% for 6-12 y/o
10 275
7.5-8.5% for <6 y/o
11 310
12 345
 ) ) ) ) )
)))) ))))
CGM
S
 Insulin Pump Candidates

• Highly motivated
• Willing to perform frequent blood glucose
monitoring
• Good control on basal/bolus regimen
• Proficient at carbohydrate counting
• Proficient at adjusting insulin doses with
I:CHO and correction factor
 Insulin Pump

• Only NovoLog or Humalog insulin

• Hourly basal rate:
1. 80% of total daily insulin dose
2. Divided by 2
3. Divide by 24
• Same I:CHO and correction factor
 Insulin Pump
• Advantages
– Mimics physiologic pancreatic secretion
– Lifestyle
– Accurate dosing
– Less hypoglycemia
• Disadvantages
– No depot to protect from DKA
– Labor intensive
– Expensive
New Directions: Inhaled Insulin
 Kuliah semester 4

SKRINING HIPOTIROID KONGENITAL

Harjoedi Adji Tjahjono, dr, SpA(K)

FKUB / RSUD Dr. Saiful Anwar Malang, 2021
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51
 PENDAHULUAN
Hormon tiroid :
• Penting untuk pertumbuhan dan perkembangan

Hipotiroid kongenital:
• Krn kurang / tidak adanya hormon tiroid sejak lahir.
• Penyebab retardasi mental yang dapat dicegah

Keterlambatan diagnosis
menyebabkan kerusakan otak yang irreversibel
Skrining hipotiroid kongenital
penting untuk mencegah keterlambatan diagnosis
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 EPIDEMIOLOGI
• Di AS
- 1: 4.000 kelahiran
• Internasional
- 1: 3.000-4.000 kelahiran
- Timur tengah 1: 1.400-2.000 kelahiran
• Rasio anak perempuan dan lelaki 2:1
• Anak dengan sindrom Down 35x lebih tinggi
dibandingkan anak normal.
• INDONESIA
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 Skrining bayi baru lahir:
• Amerika : • Singapura:
– 29 penyakit – 20 penyakit
– 4 juta bayi / tahun – 400.000 bayi / tahun
– Cakupan: 99,9 % – Cakupan: 99,95 %
– 12.500 bayi – 1981 riset, 1990
ditemukan dengan skrining nasional
kelainan bawaan

Indonesia:
???
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 DASAR HUKUM
1. Amandemen UUD 1945 pasal 28B ayat 2, menyatakan bahwa setiap anak berhak atas kelangsungan hidup, tumbuh dan
berkembang serta berhak atas perlindungan dari kekerasan dan diskriminasi;

2. Undang-undang Nomor 23 tahun 2002 tentang Perlindungan Anak pada pasal 8 menyebutkan bahwa, setiap anak berhak
memperoleh pelayanan kesehatan dan jaminan sosial sesuai dengan kebutuhan fisik, mental, spiritual dan sosial.

3. Undang-undang Nomor 23 tahun 2002 tentang Perlindungan Anak pada pasal 44 menyebutkan bahwa pemerintah wajib
menyediakan fasilitas dan menyelenggarakan upaya kesehatan yang komprehensif bagi anak yang meliputi upaya promotif,
preventif kuratif dan rehabilitatif di fasilitas pelayanan kesehatan dasar maupun rujukan, agar setiap anak memperoleh
derajat kesehatan yang optimal sejak dalam kandungan;

4. Undang-undang Nomor 23 tahun 2002 tentang Perlindungan Anak pasal 46 menyatakan bahwa: Negara, pemerintah,
keluarga, dan orang tua wajib mengusahakan agar anak yang lahir terhindar dari penyakit yang mengancam
kelangsungan hidup dan/atau menimbulkan kecacatan;

5. Undang-undang Nomor 36 tahun 2009 tentang Kesehatan pasal 131 ayat 1: Upaya pemeliharaan kesehatan bayi dan
anak ditujukan untuk mempersiapkan generasi yang akan datang yang sehat, cerdas, dan berkualitas serta untuk
menurunkan angka kematian bayi dan anak;

6. Undang-undang Nomor 44 Tahun 2009 Tentang Rumah Sakit;

7. Peraturan Pemerintah Nomor 32 tahun 1996 tentang Tenaga Kesehatan;
8. Peraturan Menteri Kesehatan Nomor 269/Menkes/Per/III/2008 tentang Rekam Medis;
9. Peraturan Menteri Kesehatan Nomor 411/Menkes/PER/III/2010 tentang Laboratorium Klinik;
10. Peraturan Menteri Kesehatan Nomor 43 tahun 2013 Tentang Cara Penyelenggaraan Laboratorium Klinik Yang Baik;
11. Peraturan Menteri Kesehatan Nomor 25 tahun 2014 tentang Upaya Kesehatan Anak;
12. Keputusan Menteri Kesehatan Nomor 128/Menkes/SK/II/2004 tentang Kebijakan Dasar Pusat Kesehatan Masyarakat;
13. Keputusan Menteri Kesehatan Nomor 370/Menkes/SK/III/2007 tentang Standar Profesi Ahli Teknologi Laboratorium
Kesehatan;
14. Keputusan Menteri Kesehatan Nomor 605/Menkes/SK/VII/2008 tentang Standar Balai Laboratorium Kesehatan dan Balai
Besar Laboratorium Kesehatan;
15. Keputusan Menteri Kesehatan Nomor 298/Menkes/SK/III/2008 tentang Akreditasi Laboratorium.
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16. PERMENKES 78 th 2014 tentang Skrining Hipotiroid Kongenital
56
MANIFESTASI KLINIS

Lahir
• Tampak seperti bayi lainnya
• Post-term (lebih bulan,
biasanya
> 42 minggu)
• Berat badan > 4 kg

• Sebagian besar tidak

tampak gejala saat lahir
• ≈ tidak spesifik

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MANIFESTASI KLINIS

Edema
(sembab)

Makroglosi
a

Hernia
umbilikalis

58
 DIAGNOSIS

• Anamnesis dan pemeriksaan fisis

• Fungsi hormon tiroid
– fT4
– TSH
• Radiologis :
– Bone age
– X-Ray lutut dan kaki

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 TERAPI
Substitusi hormon tiroid
• L-Tiroksin

Berapa lama??
• Seumur hidup

Dosis inisial terapi L‐tiroksin

• 10 ‐ 15 ug/kg/hari

60
(AAP.
 PROGNOSIS
Tanpa terapi dini
• Retardasi mental
• Gangguan koordinasi motorik
• Hipotonia
• Ataksia
Makin dini diagnosis + terapi , Makin baik prognosisnya

Usia Mulai IQ > 85 Rata-rata IQ

Terapi
0-3 bulan 78% 89 (64-107)
3-6 bulan 19% 71 (35-96)
> 6 bulan 0% 54 (25-80)
(Klein AH, et al. (J Pediatr 1972; 81: 912-915)
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 Skrining Hipotiroid Kongenital
di Malang
• 2018: bayi baru lahir: 12.018 bayi
• Biaya:
– APBN
– APBD
– DAK (Dana Alokasi Khusus)
• Rp 55.000 x 12.018 = Rp. 660.990.000
• Oleh: Faskes pemerintah dan swasta
(50 %)

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63
 KESIMPULAN
Hormon tiroid penting untuk pertumbuhan
dan perkembangan

Hipotiroid kongenital adalah penyebab

tersering retardasi mental yang dapat
dicegah

Manifestasi hipotiroid kongenital pada

neonatus tidak spesifik sehingga dapat
menyebabkan keterlambatan diagnosis
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Terima
kasih

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