1. Paediatric Endocrine Review Questions Abdulmoein Eid Al-Agha, MBBS, DCH, CABP, FRCPCH Professor of Pediatric Endocrinology, King Abdulaziz University Hospital Pediatric Department

2. A 2-year-old boy was referred for further assessment of his increasingly bow legs. His mother was known to have rickets. X- rays show bowing of the tibial shafts. The following blood measurements were obtained: calcium 2.37mmol/L, phosphate 0.13mmol/L, alkaline phosphatase 805IU/L, PTH 1.3pmol/L. Which one of the following statements is true?

3. A. This boy has 25% chance of inheriting rickets from his mother B. With this inherited form, he would be expected to be less severely affected than his mother C. A simultaneous blood and urine sample should be obtained for the measurement of phosphate and creatinine so that the renal threshold phosphate concentration can be calculated D. 1,25 dihydroxy vitamin D3 is usually normal or high

4. Hypophosphatemic rickets

5. An otherwise healthy 6-week infant presents with a generalized seizure. She is exclusively breast fed. The child is somewhat sleepy with normal examinations. Lab data: Glucose 4.1 mmol/l Sodium 141 mEq/L Calcium 1.5 mmol/l Phosphorus 2.1 mmol/l Magnesium0.8 mmol/l The most likely diagnosis is: a) Pseudohypoparathyroidism b) Hypoparathyroidism c) Vitamin D deficiency d) Albright’s hereditary osteodystrophy

6. Actions of PTH 1. 2. CaPO 4 NET EFFECT 25 OH Vit D 1,25 (OH) 2 Vit D 1  hydroxylase 3. Gut

7. What is an important diagnostic consideration (i.e. what else is the child at risk for) Causes ?? Causes ??

8. Permanent hypoparathyroidism –DiGeorge syndrome (hypoparathyroidism, absence of thymus gland with T-cell abnormalities, and cardiac anomalies) is associated with abnormal development of the third and fourth pharyngeal pouches from which the parathyroids derive embryologically and represents an example of a defect in parathyroid gland development. – DiGeorge syndrome and velocardiofacial syndrome are variants of the chromosome arm 22q11 microdeletion syndrome.

9. X-linked recessive hypoparathyroidism has been associated with parathyroid agenesis and has been mapped to chromosome arm Xq26-q27, the location of a putative developmental gene. Familial cases of hypoparathyroidism due to mutations of the PTH gene located on chromosome arm 11p15 have been identified. These mutations have been both dominantly and recessively inherited.

10. The hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is associated with partial monosomy of chromosome arm 10p Mitochondrial cytopathies, such as Kearns-Sayre syndrome (external ophthalmoplegia, ataxia, sensorineural deafness, heart block, and elevated cerebral spinal fluid protein), are associated with hypoparathyroidism.

11. Autosomal dominant and sporadic gain-of- function mutations of the Calcium sensing receptor, a G-protein coupled receptor, cause hypocalcemic hypercalciuria by lowering the serum calcium concentration that is required for PTH secretion and urinary calcium reabsorption Autosomal dominant and sporadic gain-of- function mutations of the Calcium sensing receptor, a G-protein coupled receptor, cause hypocalcemic hypercalciuria by lowering the serum calcium concentration that is required for PTH secretion and urinary calcium reabsorption These individuals must be differentiated from individuals with true hypoparathyroidism because treatment with active vitamin D (calcitriol) can cause nephrocalcinosis and renal insufficiency by exacerbating the already high urinary calcium excretion These individuals must be differentiated from individuals with true hypoparathyroidism because treatment with active vitamin D (calcitriol) can cause nephrocalcinosis and renal insufficiency by exacerbating the already high urinary calcium excretion

12. Sanjad Sakati syndrome (SSS) is an autosomal recessive disorder found exclusively in people of Arabian origin. Sanjad Sakati syndrome (SSS) is an autosomal recessive disorder found exclusively in people of Arabian origin. It was first reported from the Kingdom of Saudi Arabia in 1988 as a newly described syndrome mainly from the Middle East and the Arabian Gulf countries. It was first reported from the Kingdom of Saudi Arabia in 1988 as a newly described syndrome mainly from the Middle East and the Arabian Gulf countries. Children affected with this condition are born small for gestational age and present with hypocalcemic tetany or seizures due to hypoparathyroidism at an early stage in their lives. Children affected with this condition are born small for gestational age and present with hypocalcemic tetany or seizures due to hypoparathyroidism at an early stage in their lives. They have typical physical features, namely; long narrow face, deep set small eyes, beaked nose, large floppy ears, micrognathia, severe failure to grow both intrauterine and extra uterine and mild to moderate mental retardation. They have typical physical features, namely; long narrow face, deep set small eyes, beaked nose, large floppy ears, micrognathia, severe failure to grow both intrauterine and extra uterine and mild to moderate mental retardation.

14. A newborn screening tests showed the following: TSH27  IU/ml fT418 nmol/l This baby: a)Has congenital hypothyroidism and should be referred to a congenital hypothyroidism treatment center b)Will likely develop mental retardation if untreated c)Likely does not have any thyroid abnormality d)Has an altered hypothalamic set-point for T4 e)Should be started on thyroxin replacement immediately

16. Congenital hypothyroidism  Thyroid dysgenesis/agenesis  Prevalence 1 in 4,000 [Whites 1 in 2,000; Blacks 1 in 32,000]  2:1 female to male ratio  Clinical features include: hypotonia, enlarged posterior fontanelle, umbilical hernia, indirect hyperbilirubinemia  Laboratory findings: Very high TSH and low T4  Therapy: Thyroxine – keep TSH in normal range

18. 6 month female with congenital hypothyroidism..following 4 months therapy

19. A baby who was born has an abnormal newborn thyroid screen at 3 days which revealed a low T4 and normal TSH. Repeat venipuncture showed: fT4 10 pmol/l(12-22) TSH 2.3 μIU/mL (0.3-5.0) The most likely diagnosis is: a) Hypothyroidism due to dysgenesis of the thyroid gland b) Central hypothyroidism c) TBG deficiency d) Hypothyroidism from excess iodine exposure e) Normal thyroid function (as the TSH is normal)

20. Central hypothyroidism - rare TBG deficiency 1:2800 vs.

21. Thyroxine (T4)  Major product secreted by the thyroid  Circulates bound to thyroid binding proteins - thyroid binding globulin (TBG)  Only a tiny fraction (< 0.1%) is free and diffuses into tissues  When we measure T4, we measure the T4 that is bound to protein  The level of T4 is therefore largely dependent on the amount of TBG  Changes in T4 may reflect TBG variation rather than underlying pathology

22. TBG deficiency Centralhypothyroidism Free T4LowNormal TBG levelNormal Low T3RULowHigh

23. Conditions that cause alterations in TBG Increased TBGDecreased TBG InfancyFamilial deficiency Estrogen Androgenic steroid treatment - OC PillGlucocorticoids (large dose) - pregnancyNephrotic syndrome Familial excessAcromegaly Hepatitis Tamoxifen treatment

24. u 16 year 7 month, male u Growth failure x 3 1/2 years  Labs  Labs: TSH: 1008 µIU/ ml(0.3-5.0) fT4: <4 pmol/l(12-22) Antithyro Ab. 232 U/ml(0-1) A-perox Ab.592 IU/ml(<0.3) Prolactin: 29 ng/ml (2-18) Cholesterol: 406 mg/dl(100-170)

25. Start of thyroxine

26. Which one of the following statement is true regarding Graves’ ophthalmopathy? A. Graves’ disease is the least common cause of hyperthyroidism in childhood B. It results from antibodies that block the thyroid-stimulating hormone (TSH) receptor. C. Exophthalmos occurs in only one third of children. D. Ophthalmopathy is more severe in children and teens with Graves’ disease than it is in adults

27. Proptosis

28. Restlessness, poor attention span Eye changes Goiter Tachycardia, wide pulse pressure Increased GFR - polyuria Diarrhea Menstrual abnormalities Myopathy

29. Antithyroid medication (Methimazole or Propylthiouracil [PTU]) Pros : 25% remission rate every 2 years Cons: Drug induced side effects - skin rashes, agranulocytosis, lupus-like reaction Radioactive iodine ( 131 I) Pros :Easy. Essentially free of side effects Cons:Long term hypothyroidism Surgery  Blockers if markedly hyperthyroid Therapy for Graves disease:

30. Childhood thyroid eye disease Proptosis in childhood thyroid eye disease is usually associated with a hyperthyroid state The proptosis can be dramatic, but corneal exposure and restrictive myopathy occur in only some patients Neuroimaging shows enlarged extraocular muscles Most children with this complication can be treated conservatively with topical lubrication, but orbital fat decompression may be considered in patients with more advanced conditions

31. A 12-yr female has diffuse enlargement of the thyroid. Thyroid function tests suggesting hyperthyroidism Her disorder is most likely associated with which of the following pathological processes a)Infectious b)Inflammatory c)Autoimmune d)Toxic (drug) e)Neoplastic

32. Background Background: Autoimmune destruction of the thyroid Family history in 30-40% Lymphocytic infiltration Clinical Clinical: Growth failure, constipation, goiter, dry skin, weight gain, slow recoil of DTR Laboratory Laboratory: High TSH Anti-thyroglobulin and anti-peroxidase antibodies Therapy Therapy: Thyroxine Hashimoto thyroiditis

33. Three years old boy presented with goiter, short stature, deafness and symptoms suggestive of mild hypothyroidism. On examination, was having normal mentality, diffuse goiter, deaf and mute with normal CNS examination apart from sluggish reflexes. His bone age was retarded and has raised level of circulating TSH, fT4 and fT3. Three years old boy presented with goiter, short stature, deafness and symptoms suggestive of mild hypothyroidism. On examination, was having normal mentality, diffuse goiter, deaf and mute with normal CNS examination apart from sluggish reflexes. His bone age was retarded and has raised level of circulating TSH, fT4 and fT3. Among which of the following is most likely diagnosis? Among which of the following is most likely diagnosis?

34. A. Generalized resistance to thyroid hormone (GRTH) B. Pituitary resistance to thyroid hormone (PRTH) C. Pendred's syndrome D. TSH secreting Adenoma

35. Answer: Generalized resistance to thyroid hormone Generalized resistance to thyroid hormone 6/12/201635

36. Resistance to thyroid hormone (RTH) Is usually dominantly inherited Is usually dominantly inherited Is characterized by elevated fT3 &fT4 and failure to suppress TSH secretion Is characterized by elevated fT3 &fT4 and failure to suppress TSH secretion variable refractoriness to hormone action in peripheral tissues variable refractoriness to hormone action in peripheral tissues Two major forms: Two major forms: –asymptomatic individuals with generalized resistance (GRTH) –patients with thyrotoxicosis features, suggesting predominant pituitary resistance (PRTH)

37. Recognized features of RTH include failure to thrive, growth retardation and ADHD in childhood, and goitre and thyrotoxic cardiac symptoms in adults Recognized features of RTH include failure to thrive, growth retardation and ADHD in childhood, and goitre and thyrotoxic cardiac symptoms in adults The most common cause of the syndrome are mutations of the β (beta) form (THRB gene) of the thyroid hormone receptor, of which over 100 different mutations have been documented The most common cause of the syndrome are mutations of the β (beta) form (THRB gene) of the thyroid hormone receptor, of which over 100 different mutations have been documented Thyroid hormone resistance syndrome is rare, incidence is variously quoted as 1 in 50,000 or 1 in 40,000 live births Thyroid hormone resistance syndrome is rare, incidence is variously quoted as 1 in 50,000 or 1 in 40,000 live births

38. Resistance to thyroid hormone (RTH) The characteristic blood test results for this disorder can also be found in other disorders (for example TSH-oma (pituitary adenoma), or other pituitary disorders). The diagnosis may involve identifying a mutation of the thyroid receptor, which is present in approximately 85% of cases

39. Ambiguous genitalia is found in a newborn. The baby is noted to be hyperpigmented. Ultrasound demonstrates the presence of a uterus. The most useful test to aid in the diagnosis of this medical condition is : a) Testosterone b) 17-hydroxyprogesterone c) Serum sodium and potassium d) DHEAS e) DHEAS/androstenedione ratio

40. Cholesterol Pregnenolone Progesterone DOCA Corticosterone ALDOSTERONE 17 (OH) pregnenolone DHEA 17 (OH) progesteroneAndrostenedione Compound S CORTISOL TESTOSTERONE Desmolase 3-  -HSD 17-OH 21-OH 11-OH

41. If she has salt wasting congenital adrenal hyperplasia, which abnormalities are likely to develop. True or False for each a) Increased serum potassium b) Decreased serum sodium c) Decreased bicarbonate d) Decreased plasma cortisol e) Increased plasma renin activity

42. A 1-year male infant has non palpable testes. Of the following, the most appropriate next step would be a)Schedule a re-examination in 18 months b)Refer the patient for an exploratory laparotomy c)Begin therapy with LHRH d)Measure the plasma testosterone after stimulation with HCG e)Begin therapy with testosterone enanthate, 50 mg IM monthly for 3 months.

43. History 9 day old male infant 1 day history of decrease feeding, vomiting and lethargy. Examination Ill appearing infant with poor respiratory effort Vital signs: T 99  F HR 100/min BP 61/40 RR 24/min Resp:Subcostal retractions but clear to auscultation Cardiac:Regular rate and rhythm. Normal S1 and S2 Abdomen:Soft, non distended. Non tender. No HSM Neuro:Lethargic. No focal deficit Genitalia:Normal male. Bilateral descended testes

44. Laboratory data: WBC 16.7 Hb 16.4 Hct 49 Plt 537 K Na 121 K 9.3 Cl 83 CO 2 6.7 Glucose 163 BUN/Creat 33/0.2 CSF: Chemistry: Protein 74Glucose 82 Microscopy: WBC 6 RBC 100

45. Modes of presentation Classical  Simple virilizing  Virilizing with salt loss “Non classical” / Late onset

46. Therapy and evaluation of therapy Glucocorticoid (Hydrocortisone)  Monitor growth, 17-OHP, urinary pregnanetriol Fluorocortisol (Florinef 0.1 – 0.45 mg/day)  Blood pressure, plasma renin activity (PRA) Supplemental salt  Until introduction of infant food

47. History 15 year female presents with primary amenorrhea Breast development began at 10 years Examination Height: 5 ft 7 in Weight 130 lb Tanner 5 breast development Scant pubic hair What is your diagnosis?

48. 15 year female presents with primary amenorrhea Breast development began at 10 years Examination Height: 155Weight 45kg, Tanner 5 breast development Scant pubic hair Which of the following clinical features is the most likely to give you the correct diagnosis a) Blood pressure in all 4 extremities b) Careful fundoscopic examination c) Rectal examination d) Measurement of blood pressure with postural change e) Cubitus valgus and shield shaped chest

49. The earliest sign of puberty in a male is: a)Enlargement of the penis b)Enlargement of the testes c)Growth acceleration d)Pubic hair growth e)Axillary hair growth

50. XY Genotype Testosterone Estradiol Androgen Receptor Estrogen Receptor Aromatase Complete androgen insensitivity

51. 2 year old girl with breast development –No growth acceleration –No bone age advancement –No detectable estradiol, LH or FSH The most likely diagnosis is: a)Ingestion of her mother’s OCPs b)Precocious puberty c)Premature adrenarche d)Premature Thelarche e)McCune Albright Syndrome

52. Benign Premature Thelarche Isolated breast development –80% before age 2 –Rarely after age 4 Not associated with other signs of puberty (growth acceleration, advancement of bone age) Children go on to normal timing of puberty and normal fertility Benign process Routine follow-up

53. 5 year female with 6 months of pubic hair growth. Very fine axillary hair as well as adult odor to sweat. No breast development No exposure to androgens Growth chart: Normal growth without growth acceleration Most likely diagnosis: 1.Precocious puberty 2.Benign premature adrenarche 3.Non-classical congenital adrenal hyperplasia 4.Adrenal tumor 5.Pinealoma

54. Benign Premature Adrenarche Production of adrenal androgens before true pubertal development begins Presents as isolated pubic hair in mid childhood –No growth acceleration –No testicular enlargement in boys If normal growth rate, routine follow-up If accelerated growth and/or bone age advancement, screen for –CAH –Virilizing tumor (adrenal/gonadal)

55. A -5-year-old girl presents with breast enlargement and slight vaginal discharge, together with moodiness and body odor. There is no relevant past history and she is well with no headaches, visual disturbance or polydipsia. Mother and two elder sisters had early menarche at 10–11 years. On examination, her height is on the 90th centile and mid-parental height 50th centile. Examination shows Tanner stage B3, P2, A1. What is the most important diagnostic tool for this girl? A -5-year-old girl presents with breast enlargement and slight vaginal discharge, together with moodiness and body odor. There is no relevant past history and she is well with no headaches, visual disturbance or polydipsia. Mother and two elder sisters had early menarche at 10–11 years. On examination, her height is on the 90th centile and mid-parental height 50th centile. Examination shows Tanner stage B3, P2, A1. What is the most important diagnostic tool for this girl?

57. A. Observation of further progression of pubertal signs B. Confirm advancing bone age C. MRI pituitary to look for any CNS tumors D. Basal &LHRH stimulation test if needed

58. Investigations done for this case Pelvic ultrasound shows enlarged uterus with 4-mm endometrial echo, uterine length 5cm. Ovaries are 3.5mL in volume with five or six 6-mm follicles in each GnRH test shows basal/stimulated values of 2.6/20 units/L for LH, and 3.2/15 units/L for FSH of 2.6/20 units/L for LH, and 3.2/15 units/L for FSH

59. This girl has true precocious puberty This girl has true precocious puberty Onset of pubertal development before the age of 8 years in a girl with a pubertal LHRH test Onset of pubertal development before the age of 8 years in a girl with a pubertal LHRH test Idiopathic CPP is the likeliest cause but it is now regarded as good practice to carry out pituitary imaging with MRI in girls as well as boys with CPP Idiopathic CPP is the likeliest cause but it is now regarded as good practice to carry out pituitary imaging with MRI in girls as well as boys with CPP Given the age of the girl, the intensity of pubertal tempo and the behavior disturbances, suppressive therapy with an LHRH Given the age of the girl, the intensity of pubertal tempo and the behavior disturbances, suppressive therapy with an LHRH

60. Central precocious puberty (CPP) can be considered as GnRH ‐ driven precocious puberty; the physiology is the same as puberty occurring at the usual age except for age of onset. Central precocious puberty (CPP) can be considered as GnRH ‐ driven precocious puberty; the physiology is the same as puberty occurring at the usual age except for age of onset. Peripheral precocious puberty (PPP) is GnRH ‐ independent and thus includes all pubertal development that is the result of hormonal stimulation other than hypothalamic GnRH pulsatile release stimulating pituitary gonadotropin pulsatile secretion Peripheral precocious puberty (PPP) is GnRH ‐ independent and thus includes all pubertal development that is the result of hormonal stimulation other than hypothalamic GnRH pulsatile release stimulating pituitary gonadotropin pulsatile secretion

61. Etiology of central precocious puberty Gonadotropin ‐ releasing hormone (GnRH)–driven CPP can be categorized as idiopathic when there is no demonstrable abnormality and as central nervous system (CNS)–related when an abnormality could be documented on history, physical examination, or otherwise. Any insult that could affect influences on the hypothalamus may be implicated. Any insult that could affect influences on the hypothalamus may be implicated. Hypothalamic hamartomas are congenital and generally present with precocious puberty at a young age Optic glioma, occurring as an isolated finding or associated with neurofibromatosis, is a frequent cause of CNS ‐ related CPP

62. Causes of peripheral precocious puberty (PPP) in females Exogenous hormone administration, some instances of primary hypothyroidism in which the excessive thyroid ‐ stimulating hormone (TSH) stimulates the follicle ‐ stimulating hormone (FSH) receptor, oestrogen ‐ secreting ovarian or (very rarely) adrenal tumours, oestrogen ‐ secreting ovarian cysts (which also may occur in central precocious puberty), and in instances of activation mutations such as the McCune ‐ Albright syndrome

63. Premature thelarche Breast development in a 2 ‐ year ‐ old girl not associated with pubertal hormone levels with growth acceleration and significant skeletal age advance. Thelarche occurring prematurely is not associated with pubertal physical or hormonal changes. It most frequently presents during infancy or after age 6, before or after full hypothalamic ‐ pituitary ‐ ovarian axis childhood quiescence (ages 3 through 5) It may be associated with functional follicular cysts that spontaneously regress and perhaps with especially responsive breast tissue

64. Two- year old girl, brought by her mother because of bilateral breast enlargement and spotty vaginal discharges. On examination (see photo). Which is the most important confirmatory investigation you will order? Two- year old girl, brought by her mother because of bilateral breast enlargement and spotty vaginal discharges. On examination (see photo). Which is the most important confirmatory investigation you will order?

66. A. Basal LH/FSH and estrogen B. HCG C. Thyroid function test D. GnRH stimulation test

67. McCune-Albright syndrome (MAS) consists of at least 2 of the following 3 features: McCune-Albright syndrome (MAS) consists of at least 2 of the following 3 features: –polyostotic fibrous dysplasia (PFD), –café-au-lait skin pigmentation, café-au-lait –autonomous endocrine hyperfunction (e.g., gonadotropin- independentprecocious puberty). precocious pubertyprecocious puberty – Other endocrine syndromes may be present, including hyperthyroidism, acromegaly, and Cushing syndrome –Within the syndrome there are bone fractures and deformity of the legs, arms and skull, different pigment patches on the skin, and early puberty with increased rate of growth. syndrome Genetically, mutation of the gene GNAS1, on the long (q) arm of chromosome 20 at position 13.3, which is involved in G-protein signaling Genetically, mutation of the gene GNAS1, on the long (q) arm of chromosome 20 at position 13.3, which is involved in G-protein signaling mutationgeneGNAS1G-proteinmutationgeneGNAS1G-protein

68. Which one of the following is not a cause of Hirsutism in females? A. Congenital adrenal hyperplasia B. Cushing’s syndrome C. Androgen-producing ovarian tumor D. Androgen insensitivity syndrome

69. Hirsutism vs virilization Virilization includes clitoromegaly, male ‐ pattern baldness, deepening of the voice, and increased muscle mass in addition to the clinical features of Hirsutism and chronic anovulation Virilization includes clitoromegaly, male ‐ pattern baldness, deepening of the voice, and increased muscle mass in addition to the clinical features of Hirsutism and chronic anovulation The magnitude or amount of excessive hair growth can be approximated by the Ferriman ‐ Gallwey score The magnitude or amount of excessive hair growth can be approximated by the Ferriman ‐ Gallwey score With this method, the amount of hair growth in nine androgen ‐ dependent areas is compared to a standard chart (grades 1 to 4) from which a score is derived. With this method, the amount of hair growth in nine androgen ‐ dependent areas is compared to a standard chart (grades 1 to 4) from which a score is derived. Grade 1 indicates minimal terminal hair growth and grade 4 indicates dense terminal hair growth. Grade 1 indicates minimal terminal hair growth and grade 4 indicates dense terminal hair growth. Scores greater than 8 are considered to indicate hirsutism Scores greater than 8 are considered to indicate hirsutism

70. Hypertrichosis / Hirsutism Generalized hypertrichosis is a common adverse side effect of several medications. Starvation, whether due to malnutrition or anorexia nervosa, and hypothyroidism can cause acquired Hypertrichosis. Several genetic disorders can be associated with excessive generalized hair growth. Leprechaunism is characterized by Hypertrichosis and insulin resistance due to mutations in the insulin receptor gene Hirsutism is defined as excessive growth of coarse terminal hairs in androgen ‐ dependent areas such as the face, upper chest, abdomen, and back Hypertrichosis is excessive hair growth in both androgen ‐ dependent and androgen ‐ independent regions. For example, hair growth over the whole body including arms and legs would be considered Hypertrichosis because androgen ‐ independent regions are involved.

71. Ferriman ‐ Gallwey score Ferriman ‐ Gallwey score

72. A 12-year-old girl was referred with growth failure and delayed puberty. On examination her height was below the 0.4th centile and her weight was on the 25th centile. Her height velocity was 1.8 cm/year. What is the most important initial diagnostic approach? A. Celiac antibody screening B. Bone age C. Chromosomal analysis D. Thyroid function test

73. Turner syndrome This syndrome of short stature, primary amenorrhea (ovarian dysgenesis), webbed neck, lymphedema, and Cubitus valgus This syndrome of short stature, primary amenorrhea (ovarian dysgenesis), webbed neck, lymphedema, and Cubitus valgus incidence among live born female infants of one in 5000 incidence among live born female infants of one in 5000 More than half have a 45, X karyotype without evidence of mosaicism. More than half have a 45, X karyotype without evidence of mosaicism. The remainder show mosaicism and/or more complex rearrangements involving the X chromosome. The remainder show mosaicism and/or more complex rearrangements involving the X chromosome. Between 20% and 40% of girls with Turner syndrome have significant heart defects, most commonly coarctation of the aorta (70%), often bicommissural aortic valve, and aortic stenosis—lesions generally not common in girls. Between 20% and 40% of girls with Turner syndrome have significant heart defects, most commonly coarctation of the aorta (70%), often bicommissural aortic valve, and aortic stenosis—lesions generally not common in girls. In fact, girls with Turner syndrome are prone to a spectrum of left ‐ sided lesions ranging in severity from asymptomatic bicommissural aortic valve to hypoplastic left heart syndrome In fact, girls with Turner syndrome are prone to a spectrum of left ‐ sided lesions ranging in severity from asymptomatic bicommissural aortic valve to hypoplastic left heart syndrome They are also at risk for aortic dilatation, dissection, and rupture They are also at risk for aortic dilatation, dissection, and rupture

74. Short stature Categorization of children with short stature. Short stature is commonly defined as height below the third percentile. It is estimated that 10% to 15% of children whose height is below the third percentile have a pathologic growth disorder. The possibility of a growth disorder should be considered in children whose linear growth is below the third percentile, whose growth crosses two major percentile lines in a downward fashion, or who are unusually small for their family.

75. The key to the evaluation of short stature is a careful history and determination of the growth parameters. Children with a height within two standard deviations of the mean for age and a normal height velocity are unlikely to have a pathologic cause of their short stature In the history, particular attention should be directed to the birth history, the past growth pattern, parental heights, and developmental milestones as well as to nutrition and evidence of systemic disease. On physical examination, particular attention should be paid to anomalies suggestive of chromosomal disease, as well as to arm span. Preliminary investigations can include a free thyroxine (T4) and thyroid-stimulating hormone (TSH), blood urea nitrogen (BUN) or creatinine, erythrocyte sedimentation rate (ESR), complete blood count (CBC), and an assessment of skeletal maturation (bone age). karyotype should be obtained in females and in those males with significant physical anomalies karyotype should be obtained in females and in those males with significant physical anomalies

78. Three years old boy presented with goiter, short stature, deafness and symptoms suggestive of mild hypothyroidism. On examination, was having normal mentality, diffuse goiter, deaf and mute with normal CNS examination apart from sluggish reflexes. His bone age was retarded and has raised level of circulating TSH, fT4 and fT3. Three years old boy presented with goiter, short stature, deafness and symptoms suggestive of mild hypothyroidism. On examination, was having normal mentality, diffuse goiter, deaf and mute with normal CNS examination apart from sluggish reflexes. His bone age was retarded and has raised level of circulating TSH, fT4 and fT3. Among which of the following is most likely diagnosis? Among which of the following is most likely diagnosis?

79. A. Generalized resistance to thyroid hormone (GRTH) B. Pituitary resistance to thyroid hormone (PRTH) C. Pendred's syndrome D. TSH secreting Adenoma

80. Answer: Generalized resistance to thyroid hormone Generalized resistance to thyroid hormone 6/12/201680

81. Resistance to thyroid hormone (RTH) Is usually dominantly inherited Is usually dominantly inherited Is characterized by elevated fT3 &fT4 and failure to suppress TSH secretion Is characterized by elevated fT3 &fT4 and failure to suppress TSH secretion variable refractoriness to hormone action in peripheral tissues variable refractoriness to hormone action in peripheral tissues Two major forms: Two major forms: –asymptomatic individuals with generalized resistance (GRTH) –patients with thyrotoxicosis features, suggesting predominant pituitary resistance (PRTH)

82. Recognized features of RTH include failure to thrive, growth retardation and ADHD in childhood, and goitre and thyrotoxic cardiac symptoms in adults Recognized features of RTH include failure to thrive, growth retardation and ADHD in childhood, and goitre and thyrotoxic cardiac symptoms in adults The most common cause of the syndrome are mutations of the β (beta) form (THRB gene) of the thyroid hormone receptor, of which over 100 different mutations have been documented The most common cause of the syndrome are mutations of the β (beta) form (THRB gene) of the thyroid hormone receptor, of which over 100 different mutations have been documented Thyroid hormone resistance syndrome is rare, incidence is variously quoted as 1 in 50,000 or 1 in 40,000 live births Thyroid hormone resistance syndrome is rare, incidence is variously quoted as 1 in 50,000 or 1 in 40,000 live births

83. Resistance to thyroid hormone (RTH) The characteristic blood test results for this disorder can also be found in other disorders (for example TSH-oma (pituitary adenoma), or other pituitary disorders). The diagnosis may involve identifying a mutation of the thyroid receptor, which is present in approximately 85% of cases

84. 5 year old girl with pubic hair and rapid growth. She has no breast development Possible sources of androgens: 1.Liver 2.Adrenal 3.Ovary 4.Pituitary 5.Pineal

85. 5 year old girl with pubic hair and rapid growth. She has no breast development Which of the following should be considered Answer T or F for each: a)Central precocious puberty b)Congenital adrenal hyperplasia c)McCune Albright syndrome d)Benign premature adrenarche e)Adrenal tumor F T T F F

86. When does puberty occur? Classic teaching –8 -13 in girls (menarche ~ 2 years after onset of puberty) –9 -14 in boys Case: Breast development: 6 years Mother had menarche: 9.5 years

87. Why Reactivation of hypothalamic – pituitary –gonadal axis

88. Gonadatropin dependent (central) precocious puberty Clock turns on early Idiopathic > 95 % girls ~ 50 % boys > 95 % girls ~ 50 % boys –Hypothalamic hamartoma (Gelastic seizures) –NF (optic glioma) –Head trauma –Neurosurgery –Anoxic injury –Hydrocephalus

89. Treatment Why –Psychosocial –Height What –GnRH agonist

90. 7 year male presents with 6 month history of pubic and axillary hair growth as well as adult body odor. Mother thinks he is growing faster than his peers No exposure to androgens PM&SH – nil of note Mother had menarche at 12 yr Father had normal timing of his puberty Medications – none

91. Height 50 th percentile (last height at 25 th ) Weight 40 th percentile No café au lait macules No goiter Heart and lungs: normal Abdomen: Firm hepatomegaly with irregular border PrepubertalAsymmetricPubertal Adrenal source Enlarged testicle Precocious puberty

92. Height 50 th percentile (last height at 25 th ) Weight 40 th percentile No café au lait macules No goiter Heart and lungs: normal Abdomen: Firm hepatomegaly with irregular border Genitalia: Pubic hair - Tanner 2 Scrotal thinning Testes 5 ml bilaterally (pubertal >3 ml) Rest unremarkable

93. 7 year male with signs of puberty Pubertal Central precocious puberty Gonadotropins LH G Leydig cell LABS: Testosterone 48 ng/dl (<10) FSH <0.1 mIU/mL LH <0.1 mIU/mL TSH1.0 μIU/mL T4 8.9 μg/dL

94. Precocious puberty in the male Gonadotropins Prepubertal Pubertal Gonadotropin independentCentral precocious precocious pubertypuberty  HCG LH* McCune Albright syndromeGG * Familial male Precocious puberty (testotoxicosis) 1. Gonadotropin independent PP 2. Polyostotic Fibrous Dysplasia 3. Café au lait macules Leydig cell

95. Final diagnosis: Gonadotropin independent precocious puberty secondary to an βHCG secreting hepatoblastoma

96. 5 year old with breast development and growth acceleration - Estradiol 62 pg/ml (<10) - FSH <0.1 mIU/mL - LH <0.1 mIU/mL Gonadotropin independent precocious puberty

97. McCune Albright syndrome:  Café au lait macules  Gonadotropin independent precocious puberty  Polyostotic fibrous dysplasia

98. Delayed puberty Hypogonadism Hypergonadotropic Hypogonadism (↑FSH, LH) Primary gonadal failure - Chromosomal - iatrogenic (cancer therapy) - autoimmune oophoritis - galactosemia - test. biosynthetic defect Hypogonadotropic Hypogonadism (  FSH, LH) Constitutional delay Central Hypogonadism - Isolate gonad. def. - MPHD - Kallmann (anosmia) - Functional

99. A 15 yr boy has short stature and delayed puberty. He is now in early puberty (Tanner 2). His parents are of average stature. His height and weight are just below 3 rd percentile. All of the following are likely except: a)A bone age of 12 ½ years b)Growth hormone deficiency c)Adult height in the normal range d)Acceleration of growth and sexual maturation over the next 2 years. e)History of normal length and weight at birth

100. A 15 yr male has delayed puberty. He also has headaches, diplopia and increased urination. His height is < 3 rd percentille Which of the following is the most likely diagnosis? Which of the following is the most likely diagnosis? a)Diabetes mellitus b)Pinealoma c)Cerebellar tumor d)Craniopharyngioma e)Pituitary adenoma

101. A 14 yr male has tender gynecomastia (3 cm in diameter bilaterally). He is in early to mid puberty. In most cases the best management for this gynecomastia is: a)Treatment with an anti-estrogen (e.g. Tamoxifen) b)Treatment with an aromatase inhibitor c)Treatment with a dopamine agonist (bromocryptine) d)Surgery e)Reassurance

102. A 12 year female patient presents with a 4 week history of polyuria, polydipsia, and marked weight loss. She is noted to have deep, sighing respiration. Glucose is 498 mg/dL, pH is 7.06. Her electrolytes show Na 132, K 4.8, Cl 95 CO2 6 BUN 20 Creat 0.9. The MOST important initial management is: a)insulin drip 0.1 units/kg/hour b)½ Normal Saline with 40 meq K at 2x maintenance c)Bicarbonate 1 meq/kg slowly over 1 hour d)20 ml/kg normal saline bolus IV

103. Fasting2 hr post load < 100< 140 Normal ≥ 100≥ 140 < 126< 200 Pre-diabetes ≥ 126≥ 200 Diabetes Definition of diabetes

104. An obese 14 year male is found to have glycosuria. Fasting GTT is ordered and the results are as follows: TimeGlucose (mg/dL) -0-109 -120-188 This patient is at risk for the development of all the following EXCEPT a)Type 2 diabetes b)Dyslipidemia c)Hypertension d)Slipped capital femoral epiphysis e)Hashimoto thyroiditis

105. A 13 year male has new onset type 1 diabetes mellitus. Therapy for this child may include all of the following EXCEPT: a)Glargine (Lantus) and Lipro insulin (Humalog) b)Detemir (Levemir) and Aspart insulin (Novolog) c)Metformin d)Analog insulin administered via an insulin pump

106. Hypoglycemia Decreased substrate –Poor intake –Defective glycogenolysis or gluconeogenesis Increase utilization –Sepsis –Hyperinsulinism Absent counter regulatory hormones –GH –Cortisol

107. Choose correct answer A. Hypoglycemia from hyperinsulinemia B. Hypoglycemia from metabolic fuel depletion C. Both D. Neither 1. Usually preceded by ketosis 2. Brisk respones to glucagon 3. Usually responds to oral glucose B A B

108. Side effects of corticosteroids include all of the following except a)hypertension b)hypoglycemia c)decrease bone mineralization d)myopathy e)cataracts

109. What is the most likely diagnosis in this newborn infant? 1.Mother has SLE 2.Anasarca from cardiac failure 3.Systemic allergic reaction 4.Congenital nephrotic syndrome 5.Turner’s syndrome

110. 5 year old male with short stature 1.Turner syndrome 2.VATER syndrome 3.Albright’s hereditary osteodystrophy 4.Noonan syndrome 5.Goldenhar syndrome

111. A moderately obese adolescent female has irregular periods, hirsutism and acne Of the following, which is the most likely diagnosis? Of the following, which is the most likely diagnosis? a)Cushing syndrome b)Polycystic ovarian syndrome c)Virilizing adrenal tumor d)Non-classical CAH e)Hyperprolactinemia

112. Choose correct answer A. Diabetes mellitus B. Diabetes insipidus C. Both D. Neither 1. Osmolality of serum > 300 Osm/L 2. Osmolality of urine > 500 mOsm/L 3. Hypernatremia C A B 2 Na + BUN/2.8 + Gluc/18

113. A 13-year-old girl presented at clinic having been diagnosed as having hypothyroidism by her family doctor who had confirmed the diagnosis with thyroid function tests. She also had a 2-year history of a limp in her left leg. On examination she was short and obese with a goiter and other signs of hypothyroidism. She had limitation of movement of her left hip and a limp. A 13-year-old girl presented at clinic having been diagnosed as having hypothyroidism by her family doctor who had confirmed the diagnosis with thyroid function tests. She also had a 2-year history of a limp in her left leg. On examination she was short and obese with a goiter and other signs of hypothyroidism. She had limitation of movement of her left hip and a limp. What is the most likely diagnosis?

114. A. Slipped capital femoral epiphysis (SCFE) B. Chronic osteomyelitis C. Vitamin D deficiency D. Monoarticular rheumatoid arthritis

115. Slipped capital femoral epiphysis (SCFE)

116. Slipped femoral epiphysis and Hashimoto’s disease Slipped femoral epiphysis and Hashimoto’s disease Anterioposterior and ‘frog-leg’ view X-rays (an A– P) is recommended for diagnosis Anterioposterior and ‘frog-leg’ view X-rays (an A– P) is recommended for diagnosis X-ray alone may not demonstrate the slipped epiphysis) and thyroid autoantibodies. X-ray alone may not demonstrate the slipped epiphysis) and thyroid autoantibodies. Orthopedic surgeon and urgent surgery are necessary. Orthopedic surgeon and urgent surgery are necessary. An acute on chronic slippage of the epiphysis may cause a vascular necrosis of the femoral head. An acute on chronic slippage of the epiphysis may cause a vascular necrosis of the femoral head. Prophylactic pinning of the other femoral head is advocated by some surgeons. Prophylactic pinning of the other femoral head is advocated by some surgeons. Thyroxin treatment should also be started. Thyroxin treatment should also be started.

117. SCFE Both boys and girls get SCFE Both boys and girls get SCFE They are almost always approaching their teenage years or just into them (adolescents) when the problem occurs. They are almost always approaching their teenage years or just into them (adolescents) when the problem occurs. Several other factors can contribute to a child's chances of having the problem: Several other factors can contribute to a child's chances of having the problem: –Overweight children –Children with a family history of SCFE –Children who have diseases of the endocrine system, which produces hormones. Diabetes and Cushing syndrome are examples of endocrine system diseases. –Children with kidney failure, thyroid problems or growth hormone abnormalities

118. Eleven year old young boy who had presented to the clinic because of short stature. Height was much below 3 rd. percentile and weight was on 75 th. percentile. Eleven year old young boy who had presented to the clinic because of short stature. Height was much below 3 rd. percentile and weight was on 75 th. percentile. Which is the following is important in your initial evaluation?

119. A. Measure parents height and calculate mid-parental height B. Assure him that his short stature is not pathological C. Admit immediately to do growth hormone stimulation test D. Start short trial of growth hormone and see the response

120. Answer: Measure parent's height and calculate mid-parental height (an important initial evaluation measure in child with short stature)

121. 20 days old, baby boy was seen in a pediatric clinic for hypoglycemia. He had dysmorphic features, cleft lip and palate with a small mid-face. Both testes were palpable, but the penis was rather small. length was below the 3rd centile, weight on the 10th centile. 20 days old, baby boy was seen in a pediatric clinic for hypoglycemia. He had dysmorphic features, cleft lip and palate with a small mid-face. Both testes were palpable, but the penis was rather small. length was below the 3rd centile, weight on the 10th centile. What is your next best approach in order to reach diagnosis? A. Look for other dysmorphic features B. Admit and do critical sample during his hypoglycemia attack C. Do GH stimulation test D. Do MRI brain

124. Holoprosencephaly An infant with this malformation. An infant with this malformation. Up to one third of patients may have normal facial appearance. Up to one third of patients may have normal facial appearance. Mutations in the human sonic hedgehog (SHH) gene cause holoprosencephaly. Mutations in the human sonic hedgehog (SHH) gene cause holoprosencephaly. About one third of cases have various chromosomal abnormalities, such as trisomy 13 or 18, or deletion (7q), (13q), or (18q). About one third of cases have various chromosomal abnormalities, such as trisomy 13 or 18, or deletion (7q), (13q), or (18q). Some degree of holoprosencephaly is present in about 70% of trisomy 13 patients and 30% of those with 7q32-ter deletions. Some degree of holoprosencephaly is present in about 70% of trisomy 13 patients and 30% of those with 7q32-ter deletions. Holoprosencephaly has been seen in infants of diabetic mothers and also with a number of associations and genetic syndromes, including the autosomal recessive pseudotrisomy 13, Meckel- Gruber syndrome, and Smith-Lemli-Opitz syndrome Holoprosencephaly has been seen in infants of diabetic mothers and also with a number of associations and genetic syndromes, including the autosomal recessive pseudotrisomy 13, Meckel- Gruber syndrome, and Smith-Lemli-Opitz syndrome

125. GH deficiency Growth hormone (GH) deficiency occurs in approximately 1 per 10,000 children Growth hormone (GH) deficiency occurs in approximately 1 per 10,000 children The severely GH ‐ deficient child may present with hypoglycaemia in the newborn period, usually indicating concomitant glucocorticoid deficiency and panhypopituitarism. The severely GH ‐ deficient child may present with hypoglycaemia in the newborn period, usually indicating concomitant glucocorticoid deficiency and panhypopituitarism. After the first 6 months of life, linear growth rate slows in the GH ‐ deficient child, resulting in downward crossing of percentiles and subsequent growth retardation. After the first 6 months of life, linear growth rate slows in the GH ‐ deficient child, resulting in downward crossing of percentiles and subsequent growth retardation. The classically GH ‐ deficient child has a chubby appearance with increased peritruncal fat and decreased muscle mass. The classically GH ‐ deficient child has a chubby appearance with increased peritruncal fat and decreased muscle mass. Skeletal age is delayed, as is pubertal development in the older child. Skeletal age is delayed, as is pubertal development in the older child.

126. Diagnosis of GH deficiency A poor response to provocative tests of GH secretion (ie, demonstrating a peak serum GH level of <10 ng/mL in a polyclonal assay to two of the following stimuli: L ‐ dopa, clonidine, insulin ‐ induced hypoglycemia, arginine, glucagon) remains the gold standard for diagnosis of GH deficiency, despite the acknowledged lack of sensitivity and specificity of these studies. Useful screening blood studies for GH deficiency in the well ‐ nourished child who is otherwise healthy include measurement of serum insulin ‐ like growth factor ‐ 1 (IGF ‐ 1) and IGF binding protein ‐ 3 (IGFBP ‐ 3), the levels of which usually are low in GH deficiency. GH ‐ resistant patients have low IGF ‐ 1 and IGFBP ‐ 3 concentrations, but elevated GH levels. Circulating concentrations of GH ‐ binding protein, the product of proteolytic cleavage of the extracellular component of the GH receptor, may be low in some forms of GH resistance.

127. Which one of the following is an absolute contraindication for growth hormone replacement therapy in children? A. Active malignancy B. Proliferative retinopathy in a child with diabetes and growth hormone deficiency C. Scoliosis D. Within six months of post surgical removal of pituitary tumor

128. Answer: Active malignancy

129. Contraindications of GH therapy GH should not be used for pediatric treatment if patient's growth plates (epiphyses) are closed GH should not be used for pediatric treatment if patient's growth plates (epiphyses) are closed Active proliferative or severe non-proliferative diabetic retinopathy. Active proliferative or severe non-proliferative diabetic retinopathy. GH should not be used in patients with any evidence of any tumor GH should not be used in patients with any evidence of any tumor GH should not be used in patients pre- existing or active malignancy GH should not be used in patients pre- existing or active malignancy

130. Contraindications of GH therapy GH should not be used in patients with complication due to open heart or abdominal surgery and with acute respiratory failure GH should not be used in patients with complication due to open heart or abdominal surgery and with acute respiratory failure GH is contraindicated in severely obese patients or with respiratory impairments GH is contraindicated in severely obese patients or with respiratory impairments GH is contraindicated in patients with Prader- Willi syndrome who are severely obese or have severe respiratory impairment GH is contraindicated in patients with Prader- Willi syndrome who are severely obese or have severe respiratory impairment GH is not indicated for children with growth failure due to genetic Prader-Willi syndrome GH is not indicated for children with growth failure due to genetic Prader-Willi syndrome

131. Which one of the following is not proven adverse effect of growth hormone replacement? A. Carpal tunnel syndrome B. Arthralgia and myalgia C. Benign intracranial hypertension D. Increase incidence and recurrences of brain tumor

132. Answer: Increase incidence and recurrences of brain tumor is never documented and is not proven adverse effect of growth hormone therapy Increase incidence and recurrences of brain tumor is never documented and is not proven adverse effect of growth hormone therapy

133. GH side effects Allergic reaction Allergic reaction Ongoing injection site discomfort Ongoing injection site discomfort Pain in wrist (carpal tunnel) Pain in wrist (carpal tunnel) Curvature of the spine (scoliosis) Curvature of the spine (scoliosis) Joint pain Joint pain Puffy hands and/or feet (caused by fluid retention) Puffy hands and/or feet (caused by fluid retention) Changes in vision, a bad headache, or nausea Changes in vision, a bad headache, or nausea Hip or knee pain Hip or knee pain Limping Limping

134. Six-year-old girl was referred with growth failure, poor appetite, recurrent abdominal pain, ‘thick custard’ stools and vomiting. Six-year-old girl was referred with growth failure, poor appetite, recurrent abdominal pain, ‘thick custard’ stools and vomiting. What is the most diagnostic tool? A. Bone age B. Anti-tissue transglutaminase antibody C. Jejunal biopsy D. Serum iron and ferritin

135. Jejunal biopsy which will show villous atrophy and lymphocytic infiltrate in the lamina propria with hyperplastic crypts. This confirmed a diagnosis of celiac disease

137. Child with celiac disease Note the protuberant abdomen and the marked muscle wasting and evidence of malnutrition Children with celiac disease may exhibit no unusual findings on physical examination and rarely are as severely affected as this girl. Usually, they responded very well to a strict gluten ‐ free diet that she must follow for the rest of her life

138. A 9-year-old girl was referred because of tall stature. She has on & off headache. On examination there were no dysmorphic features. Her height was just above the 99th centile and her parents’ heights were on the 50 th and 75th centile. Pubertal development was: breast, stage 2; pubic hair, stage 3; and no menarche. Bone age was 12.4 years and final height prediction was 188 cm. A 9-year-old girl was referred because of tall stature. She has on & off headache. On examination there were no dysmorphic features. Her height was just above the 99th centile and her parents’ heights were on the 50 th and 75th centile. Pubertal development was: breast, stage 2; pubic hair, stage 3; and no menarche. Bone age was 12.4 years and final height prediction was 188 cm. Which one of the following statement is most appropriate?

139. A. Most likely familial and need to observe growth velocity B. Need to do basal and stimulated GH test C. Need to do IGF -1 D. Need to do an oral glucose tolerance test for GH suppression

140. Tall stature Children and adolescents with a height in excess of two standard deviations above the mean height for age are considered tall. Obesity can also lead to tall stature in childhood. However, in such children, puberty usually occurs early, with a resulting normal final adult height. Other causes of tall stature can include excessive secretion of growth hormone or sex hormones In the presence of excessive sex hormones, there will be early growth acceleration, initially leading to tall stature, subsequently, there will usually be early epiphyseal closure, resulting in short stature after puberty. In the presence of excessive sex hormones, there will be early growth acceleration, initially leading to tall stature, subsequently, there will usually be early epiphyseal closure, resulting in short stature after puberty.

141. An extra X or Y chromosome can also be associated with excessive linear growth, as can a spectrum of dysmorphic disorders, such as homocystinuria, Marfan syndrome, Weaver syndrome, which is accompanied by macrocephaly, large ears, and micrognathia, and Soto’s syndrome, also known as cerebral gigantism. Assessment of tall stature should begin with an evaluation of the height velocity and determination of bone age. An increased height velocity and advanced bone age suggest excessive production of sex hormones, growth hormone, or, occasionally, thyroid hormone. Familial tall stature is a normal variant and is associated with normal height velocity and tall parents Long extremities are associated with homocystinuria, Marfan’s syndrome, and Y chromosome disorders, whereas normal extremities are found in estrogen insensitivity and the other syndromes associated with tall stature. More girls than boys seek medical attention for tallness because of the perceived negative social consequences of the condition. In the rare instances in which treatment is indicated, relatively high doses of sex steroids are introduced early to advance osseous maturation.

142. Six month old male infant presented with failure to thrive, constipation. His mother was complaining of too many diaper change and urine was leaking out of diapers most of the time. On examination he was having moderate to severe dehydration. His initial sodium was high 175 mmol/l., very low urine osmolality. Which one of the following is least common cause in the differential diagnosis of this infant? Six month old male infant presented with failure to thrive, constipation. His mother was complaining of too many diaper change and urine was leaking out of diapers most of the time. On examination he was having moderate to severe dehydration. His initial sodium was high 175 mmol/l., very low urine osmolality. Which one of the following is least common cause in the differential diagnosis of this infant?

143. a) Langerhans cell histiocytosis b) X-linked recessive form of nephrogenic diabetes insipidus c) DIDMOAD syndrome d) Psychological polydipsia

144. Answer: Because the age of this infant of six months, the least common cause will be in this scenario is Psychological polydipsia

145. Central DI The three most common causes of cranial diabetes insipidus are: –brain tumor that damages the hypothalamus or pituitary gland, which accounts for 25% of cases –severe head injury that damages the hypothalamus or pituitary gland, which accounts for 16% of cases –complications that occur during brain surgery, which account for 20% of cases

146. Central DI Less common causes of cranial diabetic insipidus include: Less common causes of cranial diabetic insipidus include: –cancers that spread from another part of the body, such as the lungs or the bone marrow, to the brain –Wolfram syndrome, a rare genetic disorder that also causes sight and vision loss –brain damage caused by a sudden loss of oxygen, which can occur during a stroke or drowning –infections, such as meningitis and encephalitis, that can damage the brain

147. Which one of the following is first line treatment of acute hypercalcemia? A. Calcitonin B. Diuretics C. Intravenous hydration D. Bisphosphonate therapy

148. Answer: C

149. Which one of the following is commonest cause of 46 XX DSD? Which one of the following is commonest cause of 46 XX DSD? A. Partial AIS B. CAH (21- OH deficiency) C. Virilizing ovarian or adrenal tumors D. Placental Aromatase enzyme deficiency

150. Answer CAH (21- OH deficiency) is the major cause in 46 XX DSD not in 46 XY DSD.

151. 6/12/2016151

152. Which one of the following is commonest cause of 46 XY DSD? Which one of the following is commonest cause of 46 XY DSD? A. Testicular Aplasia / Hypoplasia B. Partial AIS C. Testosterone biosynthesis defects D. 5  - Reductase deficiency

153. Answer:PAIS

154. The following is true regarding primary adrenal failure? A. Is least commonly due to autoimmune damage to the adrenal gland B. Hemorrhage into adrenal gland due to meningococcal infection (Waterhouse- Frederickson syndrome is common cause C. The long and short synacthen tests are useful diagnostic tools in primary adrenal failure D. Management is usually by lifelong hydrocortisone administered orally at night.

155. Answer C Management is usually by lifelong hydrocortisone administered orally at night which is not true statement, hydrocortisone usually given 2-3 times daily, morning dose is usually higher than other doses except in CAH where we need to suppress early morning androgens, so night dose will be higher one. Management is usually by lifelong hydrocortisone administered orally at night which is not true statement, hydrocortisone usually given 2-3 times daily, morning dose is usually higher than other doses except in CAH where we need to suppress early morning androgens, so night dose will be higher one.

156. GOOD LUCK