Endocrine Flashcards
Low calcium, low phosphate cause?
Vitamin D deficiency
High calcium, high phosphate cause?
Vitamin D excess (Would also get low PTH)
Findings on Hypoparathyroidism bloods?
Low calcium
High phosphate
Low PTH
Causes of hypocalcemia
Transient hypocalcemia of infancy (<72hrs)
Vitamin D deficiency
Magnesium deficiency
Hypoparathyroidism
Cystic fibrosis
Pseudohypoparathyroidism
Causes of hypoparathyroidism
Thyroidectomy or parathyroidectomy
22q11 deletion syndrome (DiGeorge)!!
Autoimmune (APS1 which is associated with Addisons disease and mucocutaneous candidiasis)
Action of PTH
Activates 25,vit D to 1,25(OH)2vitD which increases calcium reabsorption and increases phosphate excretion in the kidney
Features of pseudohypoparathyroidism
PTH resistance, so PTH will be high but not effective so will get low calcium and high phosphate
Short stature
Tetany
Short 4th and 5th digits
Round facies / obesity
Developmental delay
Features of pseudopseudohypoparathyroidism
Skeletal manifestations:
- brachydactyly
- short stature
- round face
No PTH resistance, so normal PTH and calcium levels
Due to paternal imprinting of the GNAS mutation
Causes of Hypercalcemia
- Primary hyperparathyroidism
○ Causes increased bone resorption, increased renal Ca+ reabsorption and absorption of GI calcium (Via calcitriol) (usually as part of MEN) - Malignancy (PTHrP)
- Excess vitamin D
○ Too much GI calcium absorption
○ May be due to too much 1,25 vit D (calcitriol), ectopic sources of vitamin D eg from granulomatous disease and subcutaneous fat necrosis - Thiazide diuretics
○ Increased Ca++ reabsorption in distal tubule of kidney - Thyrotoxicosis
- Sarcoidosis
- Williams Syndrome
- Idiopathic infantile hypercalcemia
- Prolonged immobilisation (causes increased bone turnover)
Management of hypercalcemia
- Hyperhydration
- Bisphosphonates
- Glucocorticoids (helpful if due to too much vitamin D)
- Loop diuretics sometimes used
- calcitonin (short acting)
Features of MODY
Autosomal dominant inheritence
- need 3 generations of family members and at least one diagnosed with DM <25yrs old
- Monogenic
- Sulfonylureas first line for MODY1 and 3, no treatment needed for MODY2 usually
Features of MEN1
Neoplasia/ hyperplasia of the pancreas, parathyroid gland and anterior pituitary
- Hyperparathyroidism
- Pancreatic tumour
- Pituitary tumours, commonly prolactinomas
Features of APECED/ Autoimmune polyglandular syndrome 1 (AIRE gene mutation)
- Oral and nail candida
- Hypoparathyroidism
- Addisons disease
+/- alopecia, vitiligo and DM
Gene mutation causing pseudohypoparathyroidism (PTH resistance)?
GNAS mutation on chromosome 20q13 (maternal imprinting)
Features of MEN2a
Pheochromocytoma
Medullary thyroid cancer
Hyperparathyroidism
Features of MEN2b
Pheochromocytoma
Medullary thyroid cancer
(no hyperparathyroidism)
Mutation in Calcium sensing receptor (CaSR) -> high serum Ca+, low urinary Ca+ and inappropriately normal PTH?
Familial Hypocalciuric Hypercalcemia
Management of X-linked hypophosphatemic rickets?
Phosphate supplement (split dosing as much as possible to avoid phosphate peaks which cause secondary hyperPTH)
Calcitriol (1,25 vit D)
Burosumab (mab against FGF23 which is upregulated in this condition)
Cause of short stature in Turner syndrome
Absence of SHOX gene on X chromosome. Need 2 copies to have normal stature
How to distinguish central from peripheral precocious puberty?
Basal LH usually <0.3 in peripheral, >0.3 in central
LH:FSH ratio >1.0 is usually central
GnRH stimulation test can be done - will see an increase in LH to >5 with central PP
Features of McCune Albright Syndrome
- Cafe au lait macules (coast of Maine)
- Precocious puberty
- > presents with early PV bleeding at age 3-4 in girls (Initially GIPP then GDPP)
- Fibrous dysplasia of skeletal system, often asymmetric
Predisposing factors for T1DM
- HLA DR3 and DR4 (2-3x)
- HLA B8 and HLA-BW15
- f
What is the “honeymoon period” in T1DM?
Period of residual beta cell function, commonly in early months after diagnosis (residual beta cells can still make insulin)
Will usually have good glycaemic control with minimal insulin requirements
What is the “dawn phenomenon” in T1DM?
Normal occurrence of increased BGL between 4-7am with no preceding hypoglycaemia. It is a transient mild insulin resistance due to nocturnal GH secretion
Features of metabolic syndrome
Obesity (BMI >97th %ile)
Insulin resistance
Hypertension (BP >90th %ile)
Abnormal lipid profile (high trigs, low HDL)
Best test and management of CF-related DM
OGTT
Insulin
Management of adrenal crisis?
- Fluid bolus (0.9%NaCl)
- IVT with 5% glucose + 0.9% NaCl
- Hydrocortisone stress dose (50-100mg/m2) - has mineralocorticoid action also then taper hydrocortisone to physiologic requirements (6-8mg/m2)
- Can continue usual PO daily fludrocortisone dose (dose not need to be increased for stress)
Features of 21 hydroxylase deficiency
Low cortisol -> hypoglycaemia
Low aldosterone -> salt wasting (hyponatremia) and hyperkalemia
Excess testosterone shunting -> virilisation in females
Features of 3 beta hydroxysteroid dehydrogenase deficiency CAH
Low cortisol
Low aldosterone -> salt wasting in boys and girls
Low testosterone but high DHEA
- incomplete virilisation and hypospadias in M
- mild virilisation in F
- early pubic and axillary hair d/t DHEA
Features of 11 beta hydroxylase deficiency
Low cortisol
High mineralocorticoids (because deoxycorticosterone accumulates and this has mineralocorticoid activity) -> salt retention and hypertension
High testosterone -> virilisation
Most common cause of Cushing syndrome?
Iatrogenic (excess corticosteroids)
What causes Klinefelter syndrome
47 XXY
Occurs due to meiotic non-dysfunction with extra chromosome coming from the mother in 50% and coming from the father in 50%
Advanced maternal age is a RF
Hypogonadotrophic hypogonadism and anosmia
Kallman syndrome
What would you expect on bloods in 21 hydroxylase deficiency?
Elevated 17 OH progesterone
High renin
Aldosterone inappropriately low
Salt wasting:
- Low Na+
- High K+
What is the most common cause of congenital hypothyroidism?
Thyroid dysgenesis (abnormal thyroid gland development) resulting from agenesis, ectopia or hypoplasia …
with ectopia making up 2/3
Sensorineural hearing loss and goitre (with or without hypothyroidism)
Pendred syndrome (AR)
- due to lack of pendrin protein
Newborn screening doesn’t detect hypothyroidism caused by…
central hypothyroidism (screening tests for high TSH)
Management of hyperthyroidism
Carbimazole for 2-3yrs
- prevents TPO enzyme from coupling and iodinating the tyrosine residues on thyroglobulin -> reduced production of T3 and T4.
Beta blocker eg atenolol (block peripheral conversion of T3-T4) for 2-6wks
Radical treatment if no remission after >2yrs: radioactive iodine or thyroidectomy
Aim to get T4 to normal range
Management of Klinefelter syndrome
Need lifelong testosterone (remember they have Primary hypogonadism)
Genetic defect causing Noonan Syndrome?
Defect in PTPN 11 gene on chromosome 12q24
AD trait but has variable expression
Features of Bardet-Biedl syndrome
- Retinitis pigmentosa (causes night blindness and tunnel vision/loss of peripheral vision)
- Obesity
- ID
- Hypogonadism
- Polydactyly
- Renal defects (various)
Presentation of Prader Willi syndrome
- Hypotonia, weak cry at birth
- Initially FTT then obesity due to hyperphagia
- Low IQ
- Small penis with cryptorchidism
- Small hands and feet
- Hypogonadism
Features of Turners Syndrome
- Short stature (100%)
- Webbed neck, low posterior hairline
- Small mandible
- Prominent ears
- Broad chest with widely spaced nipples
- Cubitus valgus
- Distal radioulnar subluxation (Madelung deformity)
- Shortening of the 4th metatarsals + metacarpals
- Cardiac: bicuspid aortic valve (~50%), coarctation of Aorta (20%)
- Pelvic kidney or horseshoe kidney or double collecting system
- Hypogonadism (10-20% can have breast development)
- Autoimmune disease: thyroid disease (10-20%), coeliac disease
- SNHL
- Recurrent otitis media
How can you differentiate between Turners Syndrome and Noonan Syndrome?
Turners typically have normal IQ (IQ reduced in Noonan syndrome)
Turners causes R-sided cardiac defects (bicuspid aortic valve, CoA) whereas Noonan causes L-sided cardiac defects (eg PS)
Karyotype abnormal in Turners (usually 45X0), will be normal in Noonans
Features of complete androgen insensitivity (46 XY DSD)?
- Female external genitalia (due to resistance to testosterone and no formation of Wolffian ducts)
- Intra abdominal testes and no internal female genital organs
- Normal testosterone levels
- Breast development during puberty but no menses (obviously) or adrenarche (due to androgen resistance)
What do WAGR, Deny-Drash and Frasier syndromes all have in common?
All caused by mutations in the WT1 gene which is involved in gonadal and renal development. They can all cause:
- 46 XY DSD with ambiguous genitalia
- Renal disease (diffuse mesangial sclerosis in DD, FSGS in Frasier)
- Increased risk of gonadoblastoma
WAGR and Denys-Drash also at increased risk of Wilms tumour
What are the 3 features of septo-optic dysplasia
- Optic nerve abnormalities (hypoplasia of nerve or absence of optic chiasm)
- Agenesis or hypoplasia of corpus callosum and/or septum pellucidum
- Anterior and/or posterior hypopituitarism
What could you expect to find with an ectopic posterior pituitary bright spot?
Commonly causes anterior pituitary deficiencies. May present with panhypopituitarism or GH deficiency
Which agents could be used in a growth hormone stimulation test?
Clonidine, levodopa, insulin, glucagon or arginine
How do you differentiate SIADH from cerebral salt wasting
Both have hyponatremia
SIADH
- Euvolemia
- Low urine output
- Low urine Na+
- High ADH
- Normal ANP
Cerebral salt wasting (Due to over secretion of ANP)
- Hypovolemia
- High urine output
- High urine Na+
- Low ADH
- High ANP
Management of SIADH
- Fluid restriction
- Hypertonic saline if severe, symptomatic or resistant hyponatremia
- Tolvaptan (ADH receptor antagonist)
- Urea crystals
What is calcitriol?
Activated vitamin D: 1,25 (OH)2 vit D
25OH vit D (circulating form) -> converted to 1,25(OH)2 vit D by 1 alpha hydroxylase in the kidney (which is stimulated by PTH)
