Graves usually 10-20yrs at presentation. 6:1 female. Usually family history of thyroid or other autoimmune disease. Insidious else acute. Palpitations, diarrhoea, heat intolerance, agitation and deteriorating school performance, weight loss. 

Tremor, fidgety, hypertension, goitre (diffuse, smooth), bruit, exophthalmos (rare in kids). Storm can be triggered by infection or non-compliance. Hyperpyrexia, tachycardia. 

Differential

Neonates can get transient hyperthyroidism driven by maternal antibodies – improves after a few months.

Besides Grave disease, other causes of hyperthyroidism are solitary thyroid nodule (adenoma), multinodular goitre, TSH receptor abnormalities. 

Diagnosis

Besides TSH, do free T4 and T3. FT3 useful (T4 can be normal!) for showing T3 thyrotoxicosis (usually due to toxic nodular hyperthyroidism or early Grave).

Thyroid receptor antibodies usually positive. Do TPO also.

Treatment

Carbimazole – Usually 24 months total, TFTs normalise within 12/52 and dose can then be reduced.  Neutropenia as idiosyncratic side effect (so FBC monitoring not helpful!). If mild stop temporarily. Propylthiouracil second line (liver failure, ANCA vasculitis)

Radio-iodine – avoid <10yrs. Can have storm. Need long term thyroxine. 

Surgery – total or near total excision. Risk of malignancy in remnant. Esp large gland. Hypoparathyroidism as transient side effect. Recurrent laryngeal nerve damage. Iodide used pre-operatively to help texture!

Propranolol short term e.g. 3-4 weeks

Block and replace strategy – where you add thyroxine rather than reduce carbimazole? But 2 drugs not 1!

Relapse common, 2/3 within 2yrs, in adults remission unlikely after 2 years but not true in kids. 

Malignancy risk higher in Grave regardless of management…

Should be only low levels until puberty kicks in.

Most of the research into testosterone and aggression comes from adults.

Some small studies have found a link between testosterone levels in children and aggression, particularly in boys, but not all. Similarly some studies have suggested low cortisol in association with aggression, but other studies have found links to high cortisol.

A small study of pre pubertal and pubertal children (boys and girls) found testosterone levels were associated with high moodiness and low attachment. Testosterone was also associated with low sociability, but only in the prepubertal group. 

One study suggested that the influence of these hormones can modulate the balance of aggressive tendencies and empathy, with cortisol being relevant only to boys and testosterone only to girls.

All these studies at high risk of bias.

In neonates and infants, the stretched penile length is at least 2cm in 97% of boys.

Micropenis describes a shorter penis than this, that is otherwise of normal form. Penis needs to be stretched out, and suprapubic fat pad pushed in.

Causes are hypogonadotrophic (Kallman’s syndrome, Laurence-Moon-Biedel-Bart, Prader-Willi) or hypogonadism (anorchia or testicular dysgenesis, Trisomy 21, Noonans, Klinefelter). May be part of more complex syndrome.

Differential is intersex, “buried penis” due to suprapubic fat pad (usually obese), chordee.

Neat trick is to modify a 10ml syringe by cutting off needle end and inserting plunger into cut end. Gives you scale and stretches penis!

[https://dx.doi.org/10.4274%2FJcrpe.1135]

Note puberty lines on RCPCH growth charts, for starting puberty (girls 8), delayed beginning (girls 13, boys 14) and completing (girls 16, boys 17).  Delayed completion (especially menses) also needs investigation.  Also a shaded triangle for short boys and girls during this time, to remind that probably ok if puberty not yet started, but potentially a problem if nearly completing.

In girls, rule out Turner’s syndrome.

Otherwise look for evidence of dysmorphism, that might suggest another chromosomal or genetic issue, and evidence for broader pituitary issue (midline facial defects, visual defects, poor growth, child looks younger than their age).

If not central, then must be gonadal issue – check testes, do USS scan to look at ovaries.

Blood tests then to assess pituitary hormones, particularly FSH/LH, plus oestradiol and testosterone.

In girls with amenorrhoea but normal pubertal progression, haematocolpos due to imperforate hymen presents with abdominal pain, urinary retention.

Excessive cortisol due to an ACTH secreting tumour. In children, Cushing’s syndrome usually due to steroid treatment.

Manifests as dramatic weight gain, usually with angry striae, growth arrest (in terms of height), change in facial appearance, buffalo hump, hypertension.

These findings are hard to spot given that obesity with striae (and hypertension) in children common. Main clue is height centile below mean (and below MPH). Delayed bone age also a clue, as both of these things tend to be above normal in obese children.

Investigation is tricky as pituitary adenomas are not always seen on MRI and petrosal sinus sampling for cortisol is sometimes required! Even exclusion is tricky, requiring 24hr urinary cortisol collection over 3 days, low dose dexamethasone suppression testing.

CRH test done as part of work up, to see if ACTH is ectopic, which is exceptionally rare. Increased response to CRH test is almost diagnostic for Cushing’s though! High dose dexamethasone suppression rarely done.

Cortisol over 800 excludes a problem, normal response to Syncathen test (ACTH) at 1 hr should be over 470nmol/l (over 6yrs), 650 (under 6yrs).

Primary adrenal insufficiency – congenital adrenal hyperplasia (mostly 21OH deficiency), else autoimmune, genetic, infiltrative, adrenleukodystrophy (and exogenous steroid suppression).

Classic Addisonion picture – low sodium, high potassium, hyperpigmentation (can look slim and tanned, so misleadingly healthy!).

Physiological hydrocortisone replacement =10mg/m2/d in 3-4 divided doses.  Medication alert bracelet recommended, in case of crisis.  Monitor growth, BP.

If unwell, double HC dose (if varying doses, double highest dose) and give it three times daily. IM if necessary, +/- infusion.