Table 5.

Endocrinopathies: Recommendations for PROS

Hypoglycaemia		Growth Hormone and other Pituitary Deficiencies
Screening and Diagnosis
Suggestive signs and symptoms	It is important to raise awareness among parents and caregivers that episodic irritability, loss of tone, loss of consciousness, or seizures may be wholly attributable to, or exacerbated by, hypoglycaemia. These are most likely to occur as feeding intervals increase, or during intercurrent illness or other stress	Baseline screening	Baseline screening of thyroid function (critically including both TSH and free thyroxine determination) in all patients with MCAP or other forms of PROS with brain involvement (see Table 1)
Endocrine supervision	Symptoms suggestive of periodic hypoglycaemia should trigger an inpatient fast under endocrine supervision. Attention should be paid to obtaining the correct diagnostic samples at the time of symptoms. Confirmed hypoglycaemia should be followed up by screening of GH and cortisol secretion	Monitoring of linear growth	Where there is evidence of linear growth retardation, IGF1 and IGFBP3 should be measured. If these are low, then a provocative test of GH secretion should be undertaken in accord with local endocrine practice and taking into consideration clinical indicators for use of insulin in epilepsy
Inpatient fasting	There is insufficient evidence to justify inpatient fasting without suggestive symptoms. However, hypoglycaemia is a particular risk in some circumstances, when less invasive screening using continuous glucose monitoring (CGM) is warranted. If CGM is not accessible or suitable, capillary plasma glucose monitoring during symptoms can be considered. We suggest that specialist endocrine opinion is sought during (a) evaluation of seizures and (b) prior to sedation, e.g. for neuroimaging, as some CGM devices are incompatible with MRI.	Patients with proven hypoglycaemia	The above evaluation of the GH axis should also be undertaken in patients with proven hypoglycaemia, in which case a dynamic test of the hypothalamic-pituitary adrenal axis should also be undertaken
Treatment and monitoring
Emergency management	This is conventional, depending on severity of hypoglycemia. It may range from infusion of intravenous glucose to provision of sugar-containing drinks or snacks. Glucagon injection may also be of use	Deficiency of free thyroid hormone levels	Given the importance of thyroid function for neurodevelopment, any deficiency of free thyroid hormone should be corrected with L-thyroxine. TSH is not a suitable marker of hormone replacement in central hypothyroidism. Monitoring should rely instead on free thyroxine concentrations. There is a lack of data on the use of T3 in this group
Long term management	Preventative measures depend on aetiology of hypoglycaemia, and duration of fasting tolerated. In severe cases regular enteral or parenteral nutrition should be instituted with inclusion of overnight feeding, although modified starch preparations may progressively be used instead or as well in older patients	Deficiency of the adrenal axis	Should be corrected with cortisol. Note, however, that mild blunting of the axis may be a consequence rather than the cause of chronic hypoglycaemia due to resetting of counter-regulatory responses