Endocrinology Flashcards
What is the most common cause of childhood hypoglycemia?
Idiopathic ketotic hypoglycemia
Sick day principles for Diabetes
SICK
- Sugar: Do glucose and ketone checks every 3-4 hrs
- Insulin: take as normal
- Carbs and fluid intake
- Ketones:
- If BG is 6-14 with ketones, give insulin and 10% TDD
- If BG is 14-18, give insulin as normal
- If BG is >18, give insulin and 20% TDD
What are some genetic conditions that present with primary adrenal insufficiency?
- Idiopathic
- Autoimmune
- APECED (Autoimmune polyendocrinopathy syndrome type 1)
- Adrenoleukodystrophy
Treatment of adrenal insufficiency must include what?
- Hydrocortisone PO 10-15 mg/m²/24 hrs in 3 divided doses (or equivalent prednisone BID)
- During situations of stress, dose of hydrocortisone should be increased 2-3x
- Fludrocortisone PO 0.05-0.2 mg daily
What are the endocrinologic side effects of anabolic steroid use?
- Decreased sperm count
- Testicular atrophy
- Gynecomastia
- Menstrual irregularities
- Virilization in women
- Decreased glucose tolerance
What are the different types of calcium sensing receptor mutations?
- Gain of function: higher set point for serum Ca; leads to hypercalcemia
- Loss of function: unable to sense low Ca; leads to hypocalcemia
What are the serum thresholds for hypercalcemia?
- Ionized >1.3 mmol/L
* Total >2.55 mmol/L
Provide a differential for hypercalcemia with low PTH?
High Ca, low PTH (appropriate response) • excess calcium ingestion • vitamin D excess • thyrotoxicosis • bone malignancy • Paget's disease • adrenal insufficiency
Provide a differential for hypercalcemia with high PTH?
High Ca, high PTH (inappropriate response)
• primary hyperparathyroidism (MEN1 and MEN2A)
• tertiary hyperparathyroidism (renal failure)
• familial hypocalciuria hypercalcemia
When should children be screen for dyslipidemia?
- between age 9 and 11 and age 17 and 21
- at the age at least one risk factor is identified, then test every 1-3 years (fmhx of high cholesterol or premature CVD, obesity, PCOS, HTN, CKD, kawasaki disease, cancer, HCM, chronic inflammatory diseases like lupus)
- for diabetes: at 12 and 17
What treatment should be started for children with hypercholesterolemia?
Cornerstone of treatment is lifestyle modification
• Diet low in saturated fats, transfats, cholesterol
• Reduced consumption of simple sugars
• Increased dietary intake of fruits and veg
• 1 hr of moderate physical activity daily
• Caregivers should participate
If LDL cholesterol remains >160 mg/dL, drug therapy should be considered
What is Pendred Syndrome?
Condition in which a gene mutation leads to improper encoding of chloride-iodide transport in thyroid and cochlea
- results in familial goiter and neurosensory deafness (may be later in life)
- may cause a goiter a birth
What is the differential for neonatal goiter?
- Maternal antithyroid medication
- Teratoma (especially if lobulated, asymmetric, firm or large)
- Pedred syndrome
- Iodine-containing medication i.e. amiodarone, certain asthma medications, Li
- Iodine deficiency
When does a child:
- regain birth weight?
- double their birth weight?
- triple their birth weight?
- quadruple their birth weight?
“four”
- FOURteen days
- FOUR months
- 3 X FOUR = 12 months
- twenty FOUR months
With respect to height, what is 2 standard deviations?
8.5 cm in either direction of mid-parental height
Differential diagnosis for short stature with:
Normal Growth Velocity
Bone Age = Chronological Age
- Familial short stature
- Turner syndrome
- IUGR
- Spinal irradiation
Differential diagnosis for short stature with:
Normal Growth Velocity
Bone Age < Chronological Age
- Constitutional growth delay
* Chronic disease
Differential diagnosis for short stature with:
Reduced Growth Velocity
Bone Age < Chronological Age
- Growth hormone deficiency
- Hypothyroidism
- Hypogonadism
What is considered delayed tooth eruption and what are some potential causes?
No teeth by 13 months.
Hypothyroidism, hypoparathyroidism, familial, idiopathic, mechanical blockage (gum fibrosis, crowding), prematurity (<30 wks, <1000g)
What is the most common pituitary tumour?
Craniopharyngioma
What initial work up should be done for a boy presenting with gynecomastia?
- Estradiol
- Prolactin
- Testosterone
- TSH, free T4
- DHEAS
- Renal and liver function tests
- LH, FSH
- Beta hCG
- Consider karyotype
What are some causes of hirsutism without masculinization?
- Hyperandrogenism and anovulation - PCOS
- Hyperandrogenism without anovulation - Benign functional androgen excess
- Adult-onset adrenal hyperplasia
- Increased hair in androgen-dependent areas without measurable androgen excess - idiopathic hirsutism
How to differentiate hirsutism and masculinization?
Hirsutism is the development of terminal, mature adult hair in areas dependent/sensitive to androgen.
In masculinization you will additionally see:
• Alteration in muscle mass
• Clitoral enlargement
• Voice change
Common signs indicative of Cushing Syndrome?
- Hypertension
- Obesity
- Moon faces (plethoric with rounded face, posterior fat hump)
- Short stature
- Amenorrhea
- Abdominal striae
In acquired pituitary dysfunction, which hormone is most susceptible to injury/dysruption?
Growth Hormone
i.e. in malignancy, radiation, traumatic injury, meningitis, histiocytosis
How to confirm suspected growth hormone deficiency/insensitivity?
- Low IGF level
- Improper growth hormone stimulation test with 2 different stimulation agents (glucagon, arginine, insulin, clonidine)
- Should also check TSH as more common and thyroid hormone is a precursor needed for GH
8 medical conditions/indications for growth hormone replacement
- Noonan Syndrome
- Growth Hormone deficiency
- Turner Syndrome
- Prader Willi
- SHOX gene abnormality
- Idiopathic short stature
- Chronic renal failure pretransplant
- SGA before age 2
List 6 potential adverse effects of Growth Hormone replacement
- Primary/central hypothyroidism (on GH Tx) – periodic evaluation
- Risk adrenal insufficiency – periodic evaluation
- Risk T2DM (6x increase) – low insulin levels before treatment -> normalize during GH
- Pseudotumor cerebri
- SCFE
- Gynecomastia
- > Scoliosis
- ?Increased risk death in Prader-Willi (severe obesity, OSA likely, recent URI) :. Do Sleep study in PWS before starting GH
What is Lupron and what are the associated effects?
GnRH agonist; ongoing rather than pulsatile stimulation of LH and FSH seen during puberty
Effects:
• decrease of the growth rate, generally to age-appropriate values
• decrease of the rate of osseous maturation
• enhancement of the predicted height; actual adult height of patients followed to epiphyseal closure is approximately 1 SD less than their midparental height
• breast development may regress in those with Tanner stages II-III development; unchanged in girls with stages III-V development, or may even increase slightly because of progressive adipose tissue deposition
○ The amount of glandular tissue decreases
• pubic hair usually remains stable in girls, or may progress slowly during treatment; variable regression in boys
• menses, if present, cease
• pelvic sonography demonstrates a decrease of the ovarian and uterine size
• decrease of testicular size and in the frequency of erections
What is the definition of amenorrhea?
- Primary (absent menarche by 15yo)
* Secondary (absent menses >90d if previous N cycles vs. >6mo if Hx irregular cycles)
Differential diagnosis for abnormal uterine bleeding?
- Medications: OCPs/PCP/IUD, SSRI, antipsychotic medications, androgens, spironolactone
- Endocrine: Thyroid dysfunction, DM, Cushing, hyperprolactinemia
- Infection/PID
- Structural abnormalities i.e. polyps, urethral prolapse
- Trauma
- Bleeding disorder i.e. vWD, thrombocytopenia, vitamin K deficiency
What is the most likely cause of a false positive screen (hypothyroidism)?
• Done too early (<48h) – TSH physiologically elevated following postnatal TSH surge
What is the most likely cause of a false negative screen (for hypothyroidism)?
• Low Sn to detect central hypothyroidism (if TSH based alone; even if T4 measured, may initially be above cutoff)
What tests should be ordered for suspected hypothyroidism and how to interpret results?
Tests:
• TSH
• Free T4
• radionucleotide thyroid scan
- High TSH & low fT4 = 1e hypothyroidism [treat immediately]
- High TSH & normal fT4 = subclinical hypothyroidism [likely monitor to 6wk, no Tx immediately]
- Low/N TSH & low fT4 = central hypothyroidism [start treatment promptly unless premature OR suspected systemic etiology]
List 8 clinical symptoms of infant hypothyroidism.
List 4 Physical exam findings.
- Feeding problems
- Sluggishness,
- Lack of interest
- Choking spells when nursing
- Somnolence
- Respiratory difficulties may happen due to enlarged tongue
- Constipation is common
- Hypothermia
- Genital and extremity edema can be present
- Bradycardia
- Short extremities
- Wide-open fontanelle (especially posterior fontanelle)
- Delayed dentition
- Thick tongue
- Signs of developmental delay
- Prolongation of hyperbilirubinemia
- Bradycardia
- Umbilical hernia
- Dry scaly skin
What instructions should be given to the family with respect to thyroid replacement medications?
- Must be given in tablet form; crushed just before administration
- Do not give with soy milk/soy formula
- Do not give with iron or calcium as this can interfere with absorption
- Should be given with water on an empty stomach
- If a dose is missed, should be given double the dose the next day
What medications can lead to hypothyroidism?
- Excess iodine-containing medications: Amiodarone, nutritional supplements, expectorants
- Anticonvulsants: Phenytoin, phenobarbital, VPA
- Antithyroid medication: Methimazole, propylthiouracil
- Other: Lithium, interferon α, thalidomide
What medication should be used to treat Graves’ Disease?
Methimazole
May use propylthiouracil to treat in pregnancy as it does not cross the placenta or into breast milk
How should a thyroid nodule be investigated?
- Thyroid nodules in children are unusual and thus should be investigated, not watched
- Serum TSH (looking for hyperthyroidism) and a thyroid scan (123I or 99mTc-pertechnetate)
- Assessing for possible benign hyperfunctioning thyroid nodule
- Ultrasound
- If a discrete nodule of large size is then identified, it should be biopsied by US-guided FNA
- If biopsy is nondiagnostic, rpt
- If there is indeterminate cytology or unilateral nodules are noted, lobectomy is indicated
- If the lobectomy pathology reveals cancer, then complete thyroidectomy should be done
What are the diagnostic criteria for T1DM?
- fasting BG of >7.0
- random BG of >11.0
- abnormal glucose tolerance test
- must be on at least 2 different occasions if asymptomatic
- if symptomatic, any of those findings are adequate to make a new diagnosis of T1DM
What are the diagnostic criteria for T2DM?
- fasting BG of >7.0
- random BG of >11.0
- abnormal glucose tolerance test
• use of hemoglobin A1C is controversial, only to be used in conjunction with above tests
When should children with T1DM be screened for:
- Neuropathy
- Nephropathy
- Retinopathy
- Hypercholesterolemia
- Hypertension
- Thyroid disease
- Celiac disease
- at age 15, or as long as 5 years have passed since diagnosis, whichever is longer (q yearly)
- at age 12, or as long as 5 years have passed since diagnosis, whichever is longer (q yearly)
- at age 15, or as long as 5 years have passed since diagnosis, whichever is longer (q2 years)
- age 12 and age 17
- q 6 months
- at diagnosis and then every 2 years
- if clinically indicated
What targets should children with diabetes be aiming for with respect to their age categories?
- Hb A1C <7.5%
- 4-8 mmol/L
For everyone
What dose of glucagon should be used for children when treating a low BG?
• Glucagon dose: 10 mcg per year of age (minimum 20 mcg; maximum 150 mcg)
What are the criteria for screening for T2DM?
CPS: All of the following: • Aboriginal descent • BMI ≥ 85%ile • Age ≥10 years old
Any one of the following: • Sedentary lifestyle • Children born to mothers who had GDM • First- or second-degree relative with T2DM • Acanthosis nigricans • Dyslipidemia • Hypertension • PCOS
Canadian Diabetes Association
Consider every 2 years using a combination of an A1C and a FPG or random plasma glucose in any of the following conditions:
1. ≥3 risk factors in nonpubertal children beginning at 8 years of age or ≥2 risk factors in pubertal children:
• Obesity (BMI ≥95%ile for age and gender)
• High-risk ethnic group (e.g. African, Arab, Asian, Hispanic, Indigenous or South Asian descent)
• First-degree relative with T2DM and/or exposure to hyperglycemia in utero
• Signs or symptoms of insulin resistance (including acanthosis nigricans, hypertension, dyslipidemia, NAFLD [ALT >3X upper limit of normal or fatty liver on ultrasound])
2. PCOS
3. IFG and/or IGT
4. Use of atypical antipsychotic medications
If there is a discrepancy between the A1C and FPG or random plasma glucose, testing may be repeated or a 2-hour OGTT (1.75 g/kg; maximum 75 g) performed
When should screening for comorbidities be done in children with T2DM?
Yearly screening for retinopathy, neuropathy, nephropathy, NAFLD, hypercholesterolemia, depression, PCOS
HTN screening at least BID/TID
How to manage an ingestion of glyburide?
- IV glucose infusion
- Octreotide to prevent rebound hyperinsulinism
- Observe in hospital for at least 24 hours
What genes/gene regions are required for sex differentiation?
• SRY portion of Y chromosome: responsible for regression of mullerian structures via AMH and activating leydig and sertoli cells to produce testosterone, DHT and male androgen receptors
What is the approach to a child with abnormal/ambiguous genitalia?
- Must first decide if this is an undervirilized male or a overvirilized female
- determine if gonads are present i.e. palpable or by U/S
- may need to do U/S for internal structures
- Karyotype
- Should then rule out CAH using 17-OHP, androstenidione or other androgens and androgen precursors
- Assess gonadotropin levels
- Assess molecular genetics i.e. SRY gene
What are the clinical features of Denys-Drash Syndrome?
- ambiguous genitalia + gonadoblastoma
- renal disease (proteinuria, ESRD by age 3)
- risk of bilat Wilm’s Tumour
What are the clinical features of WAGR Syndrome?
- Wilm’s tumour
- Aniridia
- Genital abnormalities (usually in XY only)
- Retardation
What is the no. 1 DSD in females? Males?
- Congenital Adrenal Hyperplasia
- Androgen Insensitivity Syndrome (+Testes, >LH, >testosterone, female phenotype, N breast development, primary amenorrhea)
Management of CAH in times of sickness
• If fever or gastro & adequate PO intake:
○ 2-3x PO glucocorticoid dose (no change to fludrocortisone)
○ If unable to tolerate PO, prompt medical attention & IM HC dose (parents should be able to give at home, 50-100 mg/m2/dose)
• If illness & IMPAIRED PO Intake:
○ Go to ER
○ +/- IV glucocorticoids, saline, glucose
• If severe illness/major surgery:
○ IV glucocorticoids
○ <3yo: HC 25 mg IV x1, then 25-30 mg/d diq q6h or continuous
○ 3-12yo: HC 50 mg IV x1, then 50-60 mg/d div q6h or continuous
○ >12yo: HC 100 mg IV x1, then 100 mg/d div q6h or continuous
• Should have Medic-Alert bracelet
What is the definition of micropenis?
- Definition: a normally formed penis that is at least 2.5 SD below the mean in size
- Stretched penile length (measuring the distance from the penile base under the pubic symphysis to the tip of the glans)
- In a male newborn, concerning stretched length is < 1.9 cm
What is the definition of precocious puberty?
Precocious puberty is traditionally defined as the onset of secondary sexual characteristics before the age of:
• Eight years in girls
• Nine years in boys
What is the diagnostic criteria for PCOS?
- Evidence of hirsutism or hyperandrogenism
- Polycystic ovaries
- Anvoluation/Oligomenorrhea
What blood tests should be ordered in the case of hypoglycemia?
- Ketones, insulin, beta-hydroxybuterate
* Free fatty acids, Serum cortisol (random), TSH, ACTH, GH, IGF-1, blood gas, acylcarnitines, ammonia, lactate, HCO3-
