Endocrine Quiz / overview. Endocrine Quiz. Pituitary insufficiency. Genetic causes of hypopituitarism. Acquired MPHD Order of hormone loss..
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1 Endocrine Quiz / overview Michele O Connell Pituitary insufficiency Endocrine Quiz Congenital Causes. Acquired Causes. Genetic causes of hypopituitarism PROP1 POU1F1 (previously called Pit 1) Hesx1 Lhx3/Lhx4. Acquired MPHD Order of hormone loss.. GH Gonadotrophins TSH ACTH Timing of loss very variable; may appear different pre-pubertally!
2 Craniopharyngioma Diagnosis? Likely presenting features Likely subsequent course PRE-OP POST-OP GH: 75% GH: % Thyroxine: 25% Thyroxine: 65% FSH/LH: 40-80% FSH/LH: 80% ACTH/Cortisol:25% ACTH: 65% ADH: 10-25% ADH: 80%?How best to diagnose each deficiency GH TSH ACTH LH/FSH ADH Patient with established DI suddenly appears to have resolution of sx:?possible causes Other issues post treatment. Post radiotherapy Learning / cognition Thyroid cancer risk Hypothalamic damage Weight / satiety (obesity is very common) Thirst Increased daytime somnolence Temperature dysregulation Vision Congenital hypothyroidism Incidence 1 in 3-5,000 What s this? Common causes Agenesis / ectopy Dyshormonogenesis (TPO) Causes? Screening in Aus TSH based Treatment 10-15mcg/kg/day initially Aim to normalise TSH in 2/52; then dose adjust
3 MEN Components of MEN1 MEN2a MEN2b MEN1 (11q13) Tumours of the 3 Ps Parathyroid (90%) Pituitary (esp prolactinoma 20%) Pancreas (gastrinoma -40%; insulinoma 10%) Others Foregut tumours eg VIPoma, gastrinoma Skin collagenomas lipomas MEN 2 (RET gene 10q11.2) MEN 2a Medullary thyroid carcinoma Phaeochromocytoma Parathyroid hyperplasia / adenoma Other clinical variants Hirschsprung s disease Pruritic skin lesions MEN 2b Medullary thyroid carcinoma Phaeochromocytoma Mucosal neuromas (eyelids, conjunctiva, tongue, lips) Can have Marfanoid habitus Female puberty Normal age range Usual Timing of progression Timing of max GV Ht gain after menarche Timing of Total Thyroidectomy Monitoring thereafter Male puberty Pubertal variants Timing of onset Timing of max GV Problems Early Late Investigations?
4 Infant growth predominantly nutritionally driven Childhood growth predominantly GH/IGF axis dependent Growth Pubertal growth androgen/oestrogen dependent Considerable overlap PUBERTAL CHILDHOOD FETAL / INFANT General growth pointers Measuring: <2 yrs of age supine table with 2 measurers 2 yrs stadiometer mastoid elevation Proportions arm span to height (=1) Upper:Lower segments 1.7 as a neonate 1.4 by 4-5 years 1.0 by years Essential to measure growth velocity as well as absolute height Serial measurements required Mid-parental height Mid parental target range Males vs Females Males 13 cm taller - 2 yrs extra growth, higher velocity growth spurt Final 50th centile ht male 177cm, female 164 cm Relates to difference in timing and peak of growth spurt in boys and girls Common Variants Maturational delay Current Height Short Short Familial short stature Growth velocity Slow Normal Puberty Delayed Normal Bone age Delayed Appropriate Height prognosis Good Likely SS
5 Endocrine P I C N I C S Endocrine Psychosocial Iatrogenic Chromosomal Nutritional Intrauterine Chronic Disease Skeletal Turner Syndrome Features of impaired lymphatic drainage Congenital heart disease: coarctation of aorta/bicuspid aortic valve/other Need ECHO at dx & in puberty MRI base of heart as young adult Increased carrying angle at elbows Short stature Multifactorial; Often meet criteria for GH Rx SHOX haploinsufficiency i Madelung deformity Gonadal dysgenesis/pubertal failure Gonadoblastoma risk if Y chromosomal material Hearing defects Renal anomalies horseshoe kidney Hypertension multifactorial Other features: Eyes strabismus, ptosis, visual defects Short 4 th metacarpal / -tarsal Hyperconvex nails Autoimmunity Metabolic abnormalities?diagnosis Genetic basis PWS Endocrine issues Deletions / Maternal UPD of 15q11-q13 Other Endo: Short stature HH Insatiable appetite Obesity Increased T2DM Lipid abn / metabolic features Actions of PTH Bone Kidney Intestine Increased Ca resorption from bone Increased 1 α hydroxylase Increased Ca resorption Incr PO 4 excretion Indirect via calcitriol Major function prevention of hypocalcemia
6 Actions of 1,25 (OH) 2 D Intestine Bone Kidney Incr Ca & PO 4 absn Stimulates osteoclasts, inhibits osteoblasts Minimal direct effect on mineralisation Decreased PO 4 and Ca excretion Pseudohypoparathyroidism Resistance to PTH AD Biochemically: Hypocalcemia, high phosphate, high PTH No elevation of calcitriol No phosphaturia Resistance to multiple hormones Due to defective action of other peptide hormones that use the same stimulatory Gsα subunit to enhance camp Particularly TSH resistance Others: ACTH, GHRH, glucagon Learning difficulties / lower IQ AHO phenotype Subcutaneous calcifications Dental hypoplasia Mutations of the Calcium Sensing Receptor NH 2 Extracellular Photos / Clinical Diagnoses Ca Sensing Receptor Increased? Ca 2+,? PTH Familial Hypoparathyroidism Receptor activity Decreased Membrane Inactivating mutations cause insensitivity to Calcium? Ca 2+,? PTH Familial Hypocalciuric Hypercalcaemia
7 1:12,000
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