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Adrenal DisordersAnd DSDs, come back to this - Coggle Diagram
Adrenal Disorders
And DSDs
Disorders
Cortex
Excess
Iatrogenic
Adrenal tumours
Pitutary tumours
Deficiency
Medulla
Phaechromocytoma
Neuroblastoma
Cushings Syndrome
Short and fat
Causes
Iatrogeneic
Steroids (oral, inhaled, topical)
Long term glucocorticoid therapy
Nephrotic syndrome, asthma, ALL
Tumours
Cushing's disease
Pituitary tumour secreting ACTH
Adrenal tumours
Adenoma / carcinoma
Clinical Features
Symptoms
Slow growth
Fatigue
Emotional lability
Obesity
Signs
Moon face
Central obesity
Buffalo hump
Plethora
Acne
Striae
Hirsutism
Hypertension
Poor height velocity
DDx
Exogenous obesity
Increased growth rate
Tall
Early puberty
Diagnosis
ACTH
Dependent
Cushing Syndome :
Cushing's Disease
ACTH
Independant
Cushing
Syndrome
Normal
Normal 24hr urinary free cortisol
Investigations
24hr urinary free cortisol
ACTH levels
Diurnal variation in ACTH level
Low dose dexamethasone test
High dose dexamethasone suppression test
Managment
Wean steroids if exogenous
Tumour resection
Congeital Adrenal Hyperplasia (CAH)
Most common non-iatrogenic cause of
insufficient
cortisol and mineralocorticoid secretion
Pathogenesis
90% have Deficiency of 21-hydroxylase (converts progesterone to aldosterone + cortisol)
↑ Testosterone
↓ Decreased Cortisol + Aldosterone
↑ ACTH (primary cortisol deficiency)
Genetics
AR inheritance
1/ 15,000
Clinical Features
↑ Testosterone
Virilisation - Clitoral hypertrophy and variable fusion of labia
Enlarged penis
Pigmented scrotum
Tall stature
Muscular build
Early puberty
Adult body odour
Pubic hair
Ance
Adrenarche or menstrual disorder
↓ Aldosterone
Salt loosing Adrenal crisis
More common in boys - virilsation noticed in girls
Vomiting, weight loss, hypotonia and circulatory colapse, dehydration
Hypotension
Hyponatraemia
Hyperkalaemia
↓ Cortisol
Hypotension
Hypoglycaemia
↑ACTH
Hyperpigmentation
Diagnosis
MArkedly rasied metabolic precursor 17-alpha hydroxyprogesterone
Managment
Salt-losing crisis
Sodium chloride (NaCl)
Glucose
IV hydrocortisone
Hormone Replacement
Mineralocortidois in salt loss -
9-alpha fludrocortisone
Lifelong glucocorticoids -
Hydrocortisone
9-alpha fludrocortisone
Monitoring
Growth
Skeletal maturity
Plasma andorgens and 17-alphs-hydroxy-progesterone
Insuffiecient hormone replaecment causes ACTH increased, androgen excess and rapid initial growth and skeletal maturation at expense of final high
Excessive replacement leads to growth delay
Sick Day Rules
Additional hormone replacement to cover ilnness / surgery - unable to mount cortisol stress response
Addison's Disease
Associations
Other endocrine disorders
DM
Hypothyroidism
Hypoparathyroidism
Causes
Iatrogenic
Autoimmune
Clinical Features
Tired
Weight loss
Pigmentation (↑ACTH)
Vomit, drowsy
Low / normal BP
Investigations
24 urine free cortisol : Low / normal
Synacthen test (synthestic ACTH): No rise in cortisol
Addisonian Crises
↓Na+
↑K+
Hypoglycaemia
Treatment
Emergency fluids: Saline + dextrose
IV hydrocortisone (or Im / rectal)
Infants : 25mg
1-5 yrs : 50mg
6-12 yrs : 50-100mg
12+ : 100mg
Management
Maintenance of oral hydrocortisone and fludrocortisone
Sick day rules: Additional hydrocortisone
Other Causes of Adrenal Insufficiency
Haemorrhage / Infarction : Waterhouse-Friedrichson disease
Causes
Neonatal
Meningococcal septicaemia
X- l inked Adrenoleukodystrophy
Genetics
Mutations in ABCD1 gene encoding peroxisomal membrane portein ADLP - involved in transport of VLCFA ( very long chain fatty acids)
Tuberculosis
Rare
Long term Corticosteroid therapy
Conditinos
IBD
Nephrotic syndrome
Hypothalamic ACTH insufficiency +/- Hypopituitarism
Clinical features
Hypoglycaemia
Poor feeding
Jaundice
COnvulsions
Micro-penis
Low cortisol
Aquired causes
Tumour - craniopharyngioma
Trauma
Cranial irradiation
Surgery
Meningitis
Vascular insult
Adrenal Cortisol Deficiency
Congenital
Congenital adrenal Hyperplasia
Adrenal hypoplasia
ACTH insensitivity X-linked
Aquired
Addison's - autoimmune adrenal failure
Adrenoleukodystrophy - x lined cerebellar disorder
TB
Idiopathic
Disorders of Sex Development
DSD
Normal sex development
Primary gonad differentiates at 7-14 weeks
Female gonad is initially bipotential
Male phenotype
Y + SRY gene causes gonad to develop into testes
Testosterone → wolffian duct development
Mullerian inhibiting hormone (MIH) → inhibition of mullerian duct formation
5-α reductase → Converts testosterone to dihydrotestosterone
Dihydrotestosterone → Virilisation of external genitalia
Testosterone - internal genitalia
Dihydrotestosertone - external genitalia
MIH- inhibtion
Femal Phenotype
Absent Y chr → Gonads develop into ovaries (requires XX to maintain ovaries - turner's)
Phallus remains as clitorus
Congenital DSD Incidence
1/ 4,500
Investigations
Karyotype, SRY gene
Biochemistry
Adrenal function
HCG stim test → asses androgen biosynthesis
Testosterone + dihydrotestosterone levels
Radiology - Abdo USS
Exploration - biopsy
Classification of DSDs
Sex Chromosome DSD
Turners
45,X
Klinefelter syndrome
47, XXY
Chimerism
46,XX / 46, XY
46, XX DSD 👧
Disorders of Ovarian development: Gonadal dysgenesis
Adrogen excess: Congeital Adrenal Hyperplasia (CAH)
46, XY DSD 👦
Disorders of Testicular development: Gonadal dysgenesis
Androgen insufficiency: Synthesis or Receptor insensitivity
Phenotypes
Virilised Female
Maternal hormones - adrenal tumour
Maternal drugs
CAH
Incomplete male
Conditions
Testicular defect - reduced testosterone
5-α reductase deficiency
Receptor defect - Androgen insensitivity syndrome
Y chromosome genetic defect - XY/XO
HCG test
5-α reductase deficiency:
↑Testosterone
↓ Dihydrotestosterone (DHT)
Androgen insensitivity syndrome:
⇿ Testosterone
⇿ DHT
True Hermaphrodite (Ovo-testicular DSD)
Can be 46,XX or 46,XX.XY or 46XY
SRY transfer
Ambiguous genitalia + problems at puberty
Gonadotrophin Insufficiency
Conditions
Congenital Pituitary Dysfunction
Prader-Willi
Clinical features
Small penis
Undecended testis
Management
Choice of gender
Influence:
Endocrinologist
Urologist and gynaecologist
Biochemistry, genetics, radiology
Parents
Psychologists
International experts
Appearance of external genitalia
Degree of virilisation and puberty
Accurate diagnosis
Surgical Correction is appropriat (minimal)
HRT
Psychological support
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