Endocrine Flashcards
What is normal fasting glucose
3.5 - 5.6 mmol/L
What is normal post prandial glucose
< 7.8 mmol/L
What Is prediabetic fasting glucose
< 7.0 mmol/L
What is prediabetic post prandial glucose
> 7.8 - <11.0 mol/L
What is diabetic fasting glucose
equal to or greater than 7.0 mmol/L
What is diabetic post prandial/random glucose
equal to or greater than 11.0 mmol/L
What is diabetes
A chronic condition characterised by hyperglycaemia
What is Type 1 Diabetes
Autoimmune condition characterised by the destruction of B-Cells in the islets of Langerhans therefore no insulin production
What is Type 2 Diabetes
Progressive insulin secretory defect:
- Very low insulin production
- Insulin Resistance
How do you treat Type 1 diabetes
Insulin
How do you treat Type 2 diabetes
With Insulin &/or Diet and Exercise
What are the important genetic factors behind Type 1 diabetes
Fathers with type I diabetes transmit diabetes to their offspring 2-3 times more frequently than mothers with type I diabetes
What are the important genetic factors behind Type 2 diabetes
Type 2 has higher risk of transmission to offspring than Type 1
What does insulin do
- Stimulates uptake of glucose from blood into tissue cells of muscle, kidney and fat
- Liver: reduces hepatic glucose output by glycogenolysis and reduces gluconeogenesis
- Regulates the release of glucagon
What does low blood sugar stimulate the release of and what does it do
Glucagon - increases hepatic glucose output by increasing glycogenolysis and gluconeogenesis and reduces peripheral glucose uptake
What is a serious consequence of untreated T1DM in children
Diabetic Ketoacidosis
What happens in DKA
- Absent glucose - means there is no regulation of glucagon or Blood Glucose
- Glucagon leads to unregulated gluconeogenesis stimulates break down of fat stores leading to the production of fatty acids
- These fatty acids are converted in the liver to Ketones
- All this leads to increased ketones and glucose in the blood
- Ketones lead to acidosis
How does diabetes present
- Weight Loss +/- infection
- Increased thirst/polydipsia
- Polyuria
- Lethargy
- Poor Growth
What does DKA present with
Increased Ketones:
- Acidosis- Cellular Dysfunction and Cerebral Oedema, kidney failure
- Vomiting - Fluid & Electrolyte depletion leading to cerebral oedema and shock
- Osmotic Diuresis - Fluid and Electroltye depletion (large deficits of Na+, K+ and water) leadings to cerebral oedema and shock
Increase Glucose:
1. Osmotic Diuresis - Fluid and Electrolyte Depletion leading to cerebral oedema and shock
How do you manage DKA
Fluid Replacement Give IV insulin Monitor Glucose hourly Monitor electrolytes especially K+ hourly Very strict fluid balance Hourly neuro obs
What is Hypoglycaemia
Deficiency of glucose in the blood stream most commonly caused by insulin therapy
What are the symptoms of hypoglycaemia
Hunger Sweating Pallor Anxious Irritable Nauseous Tachycardia/Palpitations
What can happen if hypoglycaemia is left untreated
Neuroglycopenic Symptoms: Dizzy Headache Confused Drowsy Personality change seirzures/ coma
How is a mild/moderate Hypo managed
fast acting carb: Glucose Tablets, Juice/Fizzy drink
Glucogel
How is severe Hypo e.g unconscious managed
Glucagon injection IM or SC
What are important things to monitor in someone with diabetes
HbA1c - <42 (diabetic >48)
AI screening
Education - alcohol, contraception
Examination - eyes, feet, urine/kidney function, BP, injection sites,
What are the causes of Hypothyroidism in children
Congenital:
Athyreosis,
Thyroid Dysgenesis,
Thyroid Dyschormonogenesis
Acquired: Prematurity, Hashimotos Thyroiditis - AI Hypopituitarism, Trisomy 21 Low iodine in developing countries
What are the signs of Hypothyroidism
- prolonged neonatal jaundice
- poor/slow feeding
- Bradycardia
- Hypotonia
- Dry skin
- inactivity/sleepiness
- Constipation
What can untreated hypothyroidism lead to
- Poor growth and mental development
- Low IQ
- Delayed puberty
- Short Stature
How is Hypothyroidism screened and investigated
- All babies screened at newborn blood spot test
- TSH - High or Low (if pituitary failure)
- T4 - Low
How do you treat Hypothyroidism
Levothyroxine
What is testicular Torsion
When spermatic cord twists cutting off the testicular blood supply causing ishaemia
What are the two types of testicular torsion
Extravaginal - torsion outside the tunica vaginalis - exclusive to newborns and necrotic at brith needs surgical removal
Intravaginal - twisting of spermatic cord inside tunica vaginalis cutting off blood supply - usually occurs during puberty
What are the signs and symptoms of testicular torsion
Sudden onset testicular pain and tenderness
Nausea and Vomiting
Testicular exam: Tender and Red
How is Testicular Torsion diagnosed and treated
US
Prompt surgical untwisting of testicle and sewing of testicle to scrotum
What is a factor for undescended testes
Prematurity
How are undescended testes managed
If still undescended by 6 months surgical fixation within the scrotum (orchidopexy)
What are risks associated with undescended testes
infertility
Neoplasm
What is congenital adrenal hyperplasia
Usually caused by deficiency of 21 Hydroxylase by a defect on the CYP21 gene
What is the pathogenesis of CAH
Deficiency of 21 Hydroxylase leads to inadequate production presenting with:
- Low levels of cortisol
- Increase in ACTH
- Adrenal Hyperplasia
- Increase in 17 hydroxyprogesterone leading to increase testosterone production
75% will also have aldosterone deficiency/ salt wasting form - as 21 Hydroxylase is needed for it’s synthesis:
- This is severe
- Loss of Salt
How may they present with Classic CAH
Two clinical sub-types of CAH
Salt Wasting Form - Inability to retain salt and water due to deficiency of aldosterone leading to adrenal crisis if not managed:
- Males present: normal at birth (may have small balls, large penis) but a few days after birth present with salt wasting crisis:
> Hyponatraemia
> Hyperkalaemia
> Hypoglycaemia
> Hypovolaemia
> Acidosis
- This presents with symptoms of Failure to Thrive, Vomiting, Dehydration and SHOCK and Collapse
- Girls present: at birth with ambiguous/Viralised external genitalia
But genetically female and normal internal female reproductive system, will also have salt water crisis if not diagnosed at birth
Non Salt Wasting Type/Simple Viralising: Birth: - Males may appear normal but may have large penis and small testicles - Females ambiguous/viralised genitalia - No symtoms of shock
Both Classical forms will present later:
Both: Precocious Puberty, Excessive body hair, acne, deep voice, short stature and infertility
Girls: Irregular/absent periods
How will they present with Salt wasting/non-classical CAH
A much milder form which has a later onset than classical:
- Normal external genitalia in both at birth
- Precocious Puberty
- Acne
- Infertility
- Females: irregular periods, hirsutism
- Males: Early beard growth, small balls, large penis
How is CAH diagnosed
- plasma 17 hydroxyprogesterone measurement (raised)
- &/or ACTH stimulation test
(Low cortisol in blood)
How do you manage CAH
Lifelong Glucocorticoid replacement therapy:
Glucocortcosteroid - Hydrocortisone
Mineralcorticosteroid (if salt wasting) - Fludrocortisone
Genital Reconstruction Surgery in females with ambiguous genitalia
How do you manage Adrenocortical crisis
Hydrocortisone IVI Fluids Glucose Fludrocortisone Check for Hyperkalaemia - monitor ECG - if hyperkaemia give insulin with glucose infusion
How does someone with Androgen Insensitivity Syndrome present
Genetically male but ambiguous external genitalia
- penis doesn’t form or develop
- No womb or ovaries
- Fully or partially undescended testicles
What can androgen insensitivity syndrome lead to
Gender Dysphoria
Give support and advice
When is precocious puberty
before 8 in girls
before 9 in boys
What is used to stage puberty
Tanners Staging
What is important to note in the tanners stages for boys
- Enlargement of Testes and slight hair
- Enlargement of Penis followed by thick and dark pubic hair
- Boys growth accelerates when testes volume reaches 10-12ml
What is important to note for the tanners stages for girls
- Breast development and development of pubic hair
- Girls growth accelerates when breasts have started to develop
- Stage 4 breast development is prerequisite for menarche
What is a genetic disorder characterised by isolated gonadotrophin deficiency
Hypogonadothrophic Hypogonadism
Kallmans:
Delayed or Absent Puberty with absent sense of smell
Boys may have micropenis
What is Turners Syndrome
Only one normal X chromosome Born with oedema of hands and feet Short/ Webbed of neck Low hairline Streak Gonads - Infertility CVS malformations Renal malformations (horseshoe kidney) Short Stature
What is Klinefelter syndrome
Caused by boys being born with extra X - XXY
Language delay/ Learning disability
Primary Hypogonadism/Undesended Testes - Infertility!!!
Small testes/penis and enlarged breasts
Tall
Osteoporosis
Increased risk of breast cancer
What causes short stature/ delayed puberty
- Constitutional, Slow maturation (genetic) - most common cause of delayed puberty
- Idiopathic
- Environmental – psycho-social
- Nutrition – pre- or postnatal
- Chronic disease e.g IBD, coeliac, renal CHD
- Skeletal disease
- Turner’s syndrome
- Endocrine
What can cause overgrowth but impaired final height
• Precocious Puberty • Congenital adrenal hyperplasia • McAlbright syndrome • Hyperthyroidism
What can cause overgrowth but increased final height
- Androgen/ or oestrogen deficiency/ oestrogen resistance
- GH excess
- Klinefelter syndrome (XXY) • Marfan syndrome
- (Homocystinuria)
What tests should be done for Percocious Puberty
Growth Charts Puberty Staging MRI Bone Age TFTs LH and FSH 17 hydroxyprogesterone deficiency Pelvic US
What are the two causes of percosious puberty
Central/Gonadotrophin dependent: caused by hypothalamus or pituitary leading to premature release of gonadotrophins
Gonadotrophin Independent: not caused by early release of gonadotrophin e.g tumours, CAH
What causes central percocious puberty
how is it diagnosed
How is it managed
Causes:
CNS tumours
Idiopathic
Pituitary - Gonadothrophin Releasing Tumours
Diagnosis
Raised LH and FSH
GnRH stimulation test - gold standard (LH&FSH increase after administration of GnRH)
Management:
GnRH agonist
Manage underlying cause
What causes peripheral precocious puberty/ Gonadotrophin Independent Percocious Puberty (GIPP).
How is it diagnosed
How is it managed
- ↑ Androgen production, e.g.: Ovarian cyst (most common cause), Congenital adrenal hyperplasia
- ↑ Estrogen production, e.g.: HCG-secreting germ cell tumors (e.g., granulosa cell tumor)
↑ β-HCG production: e.g., hepatoblastoma - Primary hypothyroidism
- Obesity-related precocious sexual development due to compensatory hyperinsulinemia (caused by increased insulin resistance in obesity)
Diagnosis:
High oestrogen or Testosterone production depending on tumour
Low FSH and LH
GnRH stimulation test - no change
Management:
- Remove Tumour
- Treat CAH
- Ovarian cyst should resolve itself
What is Prader - Willi
Caused by a deletion in the paternally inherited chromosome 15 or maternal uniparental disomy (both copies of 15 come from mother but both turned off due to imprinting) causes:
- Neonatal hypotonia and poor feeding
- Moderate Mental Retardation
- Hyperphagia and obesity
- Small genitalia
What is Angle-mans Syndrome
Caused by a deletion in the Maternally inherited chromosome 15 or paternal uniparental disomy causes:
- “Happy puppet” unprovoked laughing/clapping
- Microcephally
- Mental retardation
- Seizures
- Ataxia
- Broad based gait
