Endocrinology

Question 1

Phenotypic / radiological characteristics of X-linked hypophosphotaemic Ricketts (XLH)

Answer 1

Frontal bossing Craniosynestosis, tooth caries, gait abnormalities, slow growth, Fractures (in adults) Metaphyseal flaring of wrist Rachitic rosary = flaring of anterior ribs at costochondral junction Nephrocalcinosis Xray - cupping and flaring

Question 2

Outline 3 main causes of Rickets

Answer 2

Vitamin D deficiency * most common* Genetic - X-linked, AD, AR Tumour related

Question 3

Underlying genetic defect in XLH

Answer 3

PHEX mutation (sporadic) Normal function = suppress FGF23 Excessive FGF23 action –> no phosphate reabsorption in loop of henle

Question 4

How does FGF23 act?

Answer 4

Fibroblast growth factor 23 (from bone) Regulates phosphate though binding renal tubular cells to stop Na+ reabsorption –> stopping phosphate reabsorption –> phosphate wasting

Question 5

What is osteomalacia + phenotype?

Answer 5

Poor mineralisation due to reduced amount of substrate Craniotabes, bowing of bones, pseudofractures

Question 6

Management principles of XLH

Answer 6

Reduce co-morbidities and optimise growth through phosphate and Vit D replacement Dental input +++ NEW –> Burosumab = human MAb against FGF23 (neutralising) Q2 weekly - increases serum phosphate, reduces ALKP

Question 7

Differential causes of low serum phosphate - NO renal wasting

Answer 7

** DIETATRY ***

Question 8

Differential causes of low serum phosphate - RENAL wasting

Answer 8

1) High FGF23 activity = XLH (reduced renal reabsorption, reduced Vit D, reduced phosphate) 2) Normal FGF23 - High PTH, renal tubular disorders

Question 9

Cause of central precocious puberty?

Answer 9

1) Hypothalamic hamartoma - secretes LH and FSH - Puberty sometimes preceeded by gelastic seizures 2) Optic gliomas in NF1 can interupt HPG axis causing precocious puberty Mx: - GnRH agonist (zolidex)

Question 10

What is Kallmann Syndrome? - cause - clinical findings - Mx

Answer 10

Inherited disorder - hypogonadotropic hypogonaism with hyposomina/anosmia - caused by impaired migration of neurons from olfactory placode to hypothalamus –> reduced gNRH Clinically: micropenis, undescended testes, midline facial defects, solitary kidney Mx: Hormone replacement

Question 11

What is McCune-Albright Syndrome?

Answer 11

Somatic mutation of G-protein which stimulates cAMP

• fibrous dysplasias of bone, cafe-au-lait macules with “coast of Maine” border + endoctinopathies

Precocious puberty - common girls > boys due to ovarian cyst formation and autonomous oestrogen production

Mx: aromatase inhibitors/anti-oestrogen meds