Diskusi kasus_Mandiri_IKA_Endokrin_2.pptx

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1. Electrolyte Imbalance in a 2-month-old Baby Girl with Susp. Congenital Adrenal Hyperplasia Robert Moderator: dr. Catur Suci Sutrisnani , M.Kes , Sp.PK , Subsp . E.M.( K ) DK Mandiri Endokrin 2 Endokrin

2. DATABASE Baby Girl, 2-month-old Chief complaint: vomiting History of present illness: Patient had been reported of vomiting since 2 days prior to admission. Vomit was non-projectile, about 2-3 times a day and after every formula milk drink. She was then look weaker and unable to drink. She was also reported of having fever. There was no fast breathing or chest indrawing. 2

3. Past Medical History: She was born via vaginal delivery in local midwife, 1900 grams, did not cry spontaneously, and with grunting. (according to maternity book) Mother was G2P1A0 on 31 st -32 nd week of pregnancy, with premature rupture of membrane. Patient was given to an orphanage shortly after birth. Orphanage staff noticed her genitalia was strange but refrained from immediately seeking medical attention because of shortage of staff. 3 DATABASE

4. General appearance look moderately ill, less active B W: 2600 grams , H: 50 cm Weight for age : <-2SD, Height for age : <-2SD, weight faltering Vital sign HR: 160, RR: 35 tpm SpO2 : 97% room air Temp : 38.2 o C Head and neck Anemic +, icteric -, dyspneic -, cyanotic - No cervical lymph node enlargement Sunken fontanelle, sunken eyelid 4 PHYSICAL EXAMINATION

5. Thorax Cor : ictus visible and palpable at ICS V MCS, single S 1 S 2 , murmur -, gallop - Pulmo : symmetrical, S=D, vesicular, Rh -/-, Wh -/- Abdomen Soft, normal bowel sound, slow turgor No liver or spleen enlargement Extremity Edema (-/-), anemic (-) Cold acral, CRT 2 sec Genitalia Female external genitalia, clitoromegaly 5 PHYSICAL EXAMINATION

6. Examination 17/1 26/1 Reference Hemoglobin 8.3 11.8 10.2 – 12 .7 g/dl Erythro cyte 2.69 4.09 3.40 – 4.23 x 10 6 /µl Hematocrite 25.1 38.3 30.6 – 38.1 % MCV 93.3 93.6 83.4 – 96.4 fl MCH 30.9 28.9 28.0 – 32.5 pg MCHC 33.1 30.8 31.9 – 3 6.0 g/dL RDW 13.8% 13.7 12.7 – 15.1% Leu kocyte 10.52 10.91 6.48 – 13 x 10 3 /µl Thrombo cyte 409 515 214 – 459 x 10 3 / μ L Diff Count (%) 6/0/-/55/29/10 3/0/-/47/45/5 0.7-5.4/0.0-1.0/42.5-71.0/20.4-44.6/3.6-9.9 6 LABORATORY EXAMINATION Hematology

7. Examination 17/1 26/1 Reference AST 76 45 <89 U/L ALT 78 38 <29 U/L Albumin 4.44 4.15 3.8 – 5.4 g/dL Ureum 65.6 50.2 11 – 36 mg/dL Creatinine 0.51 0.45 <0.39 mg/dL eGFR (Schwartz) 40.0 46.0 7 LABORATORY EXAMINATION Clinical Chemistry

8. Examination 17/1 26/1 Reference Natrium 128 137 131 – 140 mmol/L Kalium 6.57 5.37 3.3 – 4.6 mmol/L Chloride 94 107 97 – 106 mmol/L Glucose 92 84 <200 mg/dL 8 LABORATORY EXAMINATION Clinical Chemistry

9. Examination 17/1 Reference Cortisol 60.76 166 – 507 nmol/L (morning) 73.8 – 291 nmol/L (evening) 9 LABORATORY EXAMINATION Immunoserology

10. 10 U ltrasonography Ovarium present on both side Enlargement of supra renal dextra Testes are not present

11. 11 Therapy IVFD C1:4 5 cc/hour ~ 120cc/day IV Ampicillin sulbactam 3x90mg IV Paracetamol 3x30mg ⁠PO Fludrocortisone 1x10 mcg PO Salt 7 gram/kg/day PO Zinc 1x10mg PO Vitamin A 1x2000 IU PO Vitamin B comp 1x1/4 tab PO Vitamin C 1x25 mg PO Vitamin E 1x25 IU ⁠PO Vitamin D 1x2000 IU PO Folic acid 1x1 mg Diet SF 8x30 (240cc,240kkal)

12. Data Interpretation History Taking: Non-projectile vomiting, weakness, fever, ambiguous genitalia Physical Examination: Weight faltering, anemic, sunken fontanelle and eyelid, slow turgor, cold acral, slow CRT, clitoromegaly Laboratory Examination: Normochromic normocytic anemia, azotemia with low eGFR, hyponatremia, hyperkalemia, hypochloremia, low cortisol USG: ovaries present, enlargement suprarenal dextra , no testes 12

13. Data Interpretation Patient was assessed with: Adrenal Insufficiency dt Susp. Congenital Adrenal Hyperplasia Salt Wasting type Disorder of Sex Development dt Susp. CAH dd/ Sex chromosome DSD Renal insufficiency dt Susp. AKI prerenal Electrolyte imbalance dt Susp. CAH dd/ renal loss Normochromic normocytic anemia dt endocrine disease dd/ iron deficiency dt low intake 13

14. Data Interpretation Suggestion: Karyotyping, Testosterone, Estradiol, Aldosterone, 17-OHP, Urine electrolyte, Peripheral blood smear, reticulocyte, SI, TIBC Monitoring: CBC, Cortisol, RBG, Serum electrolyte, Ureum , Creatinine, eGFR 14

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17. Adrenal Insufficiency 17 Adrenal Crisis. Ingelfinger , et al. NEJM. 2019. Adrenal insufficiency arise from an absolute or a relative deficiency of cortisol, an endogenous glucocorticoid; in that circumstance, there is insufficient tissue glucocorticoid activity to maintain homeostasis. Cortisol has a circulating half-life of 90 minutes; hence, tissues become deficient within several hours after cortisol deprivation.

18. Adrenal Insufficiency 18 Adrenal crisis: still a deadly event in the 21st century. Puar, et al. AMJMed . 2015

19. Adrenal Insufficiency 19 Adrenal Crisis. Ingelfinger, et al. NEJM. 2019.

20. Congenital Adrenal Hyperplasia 20 Williams Textbook of Endocrinology. 14 th ed. 2019 CAH comprises a group of autosomal recessive disorders caused by deficient adrenal corticosteroid biosynthesis. It results from defects in one of the steroidogenic enzymes involved in cortisol biosynthesis. In each case, there is reduced negative feedback inhibition of cortisol and, depending on the steroidogenic pathway involved, alteration in adrenal mineralocorticoid and androgen secretion. More than 90% of CAH cases are caused by 21-hydroxylase deficiency.

21. Congenital Adrenal Hyperplasia Without treatment, this form of CAH can lead to profound weakness, vomiting, diarrhea, and circulatory collapse due to adrenal crisis This result in dehydration, hypovolemia, hypotension and shock Congenital Adrenal Hyperplasia: Diagnosis and Emergency Treatment Yau M, Gujral J, New MI. 2017

22. Diagnosis Clinical spectrum of 21 – hydroxylase deficiency has quite broad forms 3 types of CAH have been described Classic salt wasting Classic simple virilizing Non Classic Congenital Adrenal Hyperplasia: Diagnosis and Emergency Treatment Yau M, Gujral J, New MI. 2017

23. Congenital Adrenal Hyperplasia 23 Williams Textbook of Endocrinology. 14 th ed. 2019

24. Congenital Adrenal Hyperplasia 24 Nelson Textbook of Pediatrics. 21 st ed. 2019.

25. Nermoen , Ingrid. “Classic Congenital Adrenal Hyperplasia.” Definitions (2020): n. pag .

26. Classic Salt Wasting Form Female with this severe, classic 21-hydroxylase deficiency are exposed to excess or high systemic level of adrenal androgen prenatally (7 weeks gestation) and then born with virilized external genitalia (large clitoris, rugated and partially fused labia majora and a common urogenital sinus in place of separate urethra and vagina) Nermoen , Ingrid. “Classic Congenital Adrenal Hyperplasia.” Definitions (2020): n. pag .

27. Classic Salt Wasting Form Classic CAH-salt wasting form Infants with renal salt wasting have poor feeding, weight loss, failure to thrive, vomiting, dehydration, hypotension, hyponatremia, and hyperkalemic metabolic acidosis progressing to adrenal crisis ( azotemia , vascular collapse, shock, and death). Adrenal crisis can occur as early as age one to four weeks. Nermoen , Ingrid. “Classic Congenital Adrenal Hyperplasia.” Definitions (2020): n. pag .

28. Nimkarn , Saroj & New, Maria. (2007). Prenatal diagnosis and treatment of congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Nature clinical practice. Endocrinology & metabolism. 3. 405-13. 10.1038/ncpendmet0481.

29. 17-Hydroxyprogesterone (17-OHP) 17-OHP is an intermediate steroid in the adrenal biosynthetic pathway from cholesterol to cortisol and is the substrate for 21-hydroxylase An inherited deficiency of 21-hydroxylase leads to greatly increased serum concentration of 17-OHP, while the absence of cortisol synthesis causes an increase in adrenocorticotropic hormone. Chormanski D, Muzio MR. 17-Hydroxylase Deficiency. [Updated 2023 Jan 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK546644/

30. 31 Subjective: Baby girl, 2-month-old with non-projectile vomiting 2-3 times a day and after every meal, ambiguous genitalia Objective: Sunken fontanelle and eyelid, slow turgor, cold acral, slow CRT, clitoromegaly Laboratory: Low cortisol Hyponatremia, hyperkalemia, hypochloremia USG: ovaries present, enlargement suprarenal dextra , no testes Adrenal Insufficiency dt Susp. Congenital Adrenal Hyperplasia Salt Wasting type Suggestion: Aldosterone, 17-OHP Monitoring: CBC, Cortisol, RBG, Serum electrolyte DATA INTERPRETATION

31. Disorders of Sexual Development (DSD) 32 Williams Textbook of Endocrinology. 14 th ed. 2019 Conditions in which chromosomal, gonadal, or anatomical sex is atypical. Represent a broad range of conditions that can present to many different health professionals at different stages of life.

32. Disorders of Sexual Development (DSD) 33 Williams Textbook of Endocrinology. 14 th ed. 2019 Chromosomal sex : the complement of sex chromosomes present in an individual (e.g., 46XY or 46XX) Gonadal sex : whether the gonadal tissue developed as a testis or an ovary Phenotypic or Anatomic Sex : the developing gonad produces several steroid and peptide hormones that mediate sexual differentiation and result in the phenotypic sex seen at birth

33. DSD – Identification 34 Williams Textbook of Endocrinology. 14 th ed. 2019

34. DSD – Identification 35 Williams Textbook of Endocrinology. 14 th ed. 2019

35. 36 Subjective: Baby girl, 2-month-old with non-projectile vomiting 2-3 times a day and after every meal, ambiguous genitalia Objective: Sunken fontanelle and eyelid, slow turgor, cold acral, slow CRT, clitoromegaly Laboratory: Low cortisol Hyponatremia, hyperkalemia, hypochloremia USG: ovaries present, enlargement suprarenal dextra , no testes Disorder of Sex Development dt Susp. CAH dd/ Sex chromosome DSD Suggestion: Karyotyping, Testosterone, Estradiol, 17-OHP Monitoring: - DATA INTERPRETATION

36. AKI is defined by an abrupt decrease in kidney function that includes, but is not limited to, ARF. It is a broad clinical syndrome encompassing various etiologies Specific kidney diseases (e.g., acute interstitial nephritis, acute glomerular and vasculitic renal diseases) Non-specific conditions ( e.g , ischemia, toxic injury); Extrarenal pathology (e.g., prerenal azotemia, and acute postrenal obstructive nephropathy) 37 KDIGO AKI. 2012. AKI

37. 38 AKI in Hospitalized Children: Comparing the pRIFLE , AKIN, and KDIGO Definitions. Clin J Am Soc Nephrol. Sutherland, 2015 AKI

38. AKI 39

39. 40 Subjective: Baby girl, 2-month-old with non-projectile vomiting 2-3 times a day and after every meal, ambiguous genitalia Objective: Sunken fontanelle and eyelid, slow turgor, cold acral, slow CRT, clitoromegaly Laboratory: Azotemia with low eGFR, BUN/Cr: 60.1 Low cortisol Hyponatremia, hyperkalemia, hypochloremia USG: ovaries present, enlargement suprarenal dextra , no testes Renal insufficiency dt Susp. AKI prerenal Electrolyte imbalance dt Susp. CAH dd/ renal loss Suggestion: 17-OHP, Urine electrolyte Monitoring: Ureum , Creatinine, eGFR, Serum electrolyte DATA INTERPRETATION

40. Anemia 41 Adrenal Crisis. Ingelfinger , et al. NEJM. 2019.

41. Anemia – Adrenal 42 Williams Textbook of Endocrinology. 14 th ed. 2019 A normocytic normochromic anemia may be seen in primary adrenal insufficiency, but the anemia may also be masked by the concomitant reduction in plasma volume that is common in this disease. In experimental animals, adrenalectomy causes a mild anemia that responds to glucocorticoid. It is postulated that the anemia is resulted from inability to utilize glucose in erythropoiesis process in bone marrow.

42. 43 Subjective: Baby girl, 2-month-old with non-projectile vomiting 2-3 times a day and after every meal, ambiguous genitalia Objective: Anemic Laboratory: Normochromic normocytic anemia, normal leukocyte, normal thrombocyte Low cortisol Normochromic normocytic anemia dt endocrine disease dd/ iron deficiency dt low intake Suggestion: Peripheral blood smear, reticulocyte, SI, TIBC Monitoring: CBC DATA INTERPRETATION

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44. Congenital Adrenal Hyperplasia 45 Williams Textbook of Endocrinology. 14 th ed. 2019 CAH comprises a group of autosomal recessive disorders caused by deficient adrenal corticosteroid biosynthesis. It results from defects in one of the steroidogenic enzymes involved in cortisol biosynthesis. In each case, there is reduced negative feedback inhibition of cortisol and, depending on the steroidogenic pathway involved, alteration in adrenal mineralocorticoid and androgen secretion. More than 90% of CAH cases are caused by 21-hydroxylase deficiency.

45. Congenital Adrenal Hyperplasia 46 Williams Textbook of Endocrinology. 14 th ed. 2019

46. Aldosterone Deficiency and Electrolyte Imbalance 47 Sharma L, Momodu II, Singh G. Congenital Adrenal Hyperplasia. [Updated 2025 Jan 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. In CAH due to 21-hydroxylase deficiency, the enzyme responsible for converting precursors into cortisol and aldosterone is either absent or impaired. This results in a reduced synthesis of both cortisol and aldosterone. In severe cases (the salt-wasting form of CAH), aldosterone levels are extremely low or absent. Aldosterone is essential for sodium reabsorption and potassium excretion in the kidneys, so its deficiency leads to significant salt loss.

47. Aldosterone Deficiency and Electrolyte Imbalance 48 Sharma L, Momodu II, Singh G. Congenital Adrenal Hyperplasia. [Updated 2025 Jan 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Hyponatremia: In salt-wasting CAH, the deficiency of the enzyme 21-hydroxylase leads to reduced production of aldosterone. This causes significant sodium loss through urine ( natriuresis ), resulting in hypovolemia and hyponatremia. The low sodium levels can lead to mild cerebral edema , which stimulates the vomiting center in the medulla oblongata, increasing the likelihood of projectile vomiting.

48. Hyperkalemia: Aldosterone deficiency also leads to potassium retention ( hyperkalemia ). Hyperkalemia can disrupt gastrointestinal smooth muscle function, causing abnormal contractions of the stomach and intestines, contributing to strong vomiting episodes such as projectile vomiting. Cortisol Deficiency and Hypoglycemia Low cortisol levels impair the body’s ability to respond to metabolic stress, including hypoglycemia . Hypoglycemia can stimulate the  chemoreceptor trigger zone  (CTZ) located in the area postrema of the brain, which plays a role in the vomiting mechanism. Additionally, low cortisol exacerbates hypotension due to aldosterone deficiency, potentially affecting brain perfusion and triggering vomiting reflexes. 49

49. Stimulation of the Vomiting Center in the Medulla Oblongata Electrolyte imbalances (hyponatremia, hyperkalemia ) and metabolic disturbances ( hypoglycemia ) provide direct and indirect stimulation to the vomiting center in the medulla oblongata via the CTZ. This activation results in sudden vomiting with high intra-abdominal pressure, characteristic of projectile vomiting. Hypovolemia and Systemic Perfusion Disturbances Hypovolemia due to fluid and sodium loss also decreases perfusion to vital organs, including the gastrointestinal tract and brain. This reduced perfusion can trigger excessive sympathetic responses, further worsening the vomiting response. 50

50. Conclusion It has been discussed a 2-m.o-baby girl with: Adrenal Insufficiency dt Susp. Congenital Adrenal Hyperplasia Salt Wasting type Disorder of Sex Development dt Susp. CAH dd/ Sex chromosome DSD Renal insufficiency dt Susp. AKI prerenal Electrolyte imbalance dt Susp. CAH dd/ renal loss Normochromic normocytic anemia dt endocrine disease dd/ iron deficiency dt low intake 51

51. Conclusion Suggestion: Karyotyping, Testosterone, Estradiol, Aldosterone, 17-OHP, Urine electrolyte, Peripheral blood smear, reticulocyte, SI, TIBC Monitoring: CBC, Cortisol, RBG, Serum electrolyte, Ureum , Creatinine, eGFR 52

52. Thank You