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AimsNICE currently recommends the use of recombinant human growth hormone (rHGH) to treat growth failure in 6 conditions based on a systematic review by Takeda et al.Growth hormone deficiency, Turner Syndrome, Prader-Willi syndrome, chronic renal insufficiency, SHOX deficiency, and children born small for gestational age with subsequent growth failure at over 4 years old.Unfortunately, there are genetic syndromes in which short stature remains a feature, yet rHGH is not currently licensed. As a result, there are a small number of children who may benefit from rHGH, yet remain unable to access it, with the subsequent theoretical risks of social isolation, educational underachievement and emotional distress associated with short stature. We hope these case reports can stimulate somewhat controversial discussions around the use of rHGH beyond its current mandate.MethodsWe present case reports from a UK hospital focussing on 2 patients with rare genetic conditions associated with short stature- Trichorhinophalangeal Syndrome and KBG Syndrome, accompanied by a summary of the current literature surrounding rHGH use in each condition.ResultsThere are 10 reported cases of rHGH use in TRPS, summarised below.Abstract G232(P) Table 1PaperGH dose (mg/kg/week)Height standard deviation score changeNaselli 1998 0.23 0 0.23 0 Stagi 2008 0.26 +0.7 in 5 years 0.26 +1.9 in 7 years Sarafoglou 2010 0.3–0.43 +1.81 in 3 years 0.34–0.54 +1.95 in 2 years Sohn 2012 0.2 +0.4 in 10 years ? 0 Merjaneh 2014 0.28 +1.0 in 2 years Riedl 2004 0.2 ? Taken together, they suggest rHGH can be of benefit, and that earlier initiation of therapy is associated with better height outcomes. More information is needed before TRPS I can be considered a firm indication, but rHGH has potential to improve height outcomes in the short term.Turning attention to KBG syndrome, there are only 2 detailled case reports of GH treatment in this condition (Reynart et al.2015). These children increased their height by 0.6 and 1 SDS within 1 year of treatment, respectively.ConclusionThis work demonstrates the clinical features of 2 rare genetic conditions, and highlights the need for further debate around the potential of rHGH in maximising growth potential, with the ultimate aim of improving quality of life for patients with rare conditions including KBG syndrome and TRPS.References. Takeda A. Recombinant human growth hormone for the treatment of growth disorders in children: A systematic review and economic evaluation. Health Technol Assess2010September;14(42):1–209.. Naselli A. Trichorhinophalangeal syndrome type I in monozygotic twins discordant for hip pathology: Report on the morphological evolution of cone-shaped epiphyses and the unusual pattern of skeletal maturation. Pediatr Radiol1998November;28(11):851–5.. Stagi S. Partial growth hormone deficiency and changed bone quality and mass in type I trichorhinophalangeal syndrome. Am J Med Genet A2008June 15;146A(12):1598–604.. Sarafoglou K, Moassesfar S, Miller BS. Improved growth and bone mineral density in type I trichorhinophalangeal syndrome in response to growth hormone therapy. Clin Genet2010December;78(6):591–3.. Sohn YB. Clinical, biochemical, and genetic analysis of two Korean patients with trichorhinophalangeal syndrome type I and growth hormone deficiency. Ann Clin Lab Sci2012Summer;42(3):307–12.. Merjaneh L1. A novel TRPS1 gene mutation causing trichorhinophalangeal syndrome with growth hormone responsive short stature: A case report and review of the literature. Int J Pediatr Endocrinol2014;2014(1):16.. Riedl S. Pronounced short stature in a girl with tricho-rhino-phalangeal syndrome II (TRPS II, Langer-Giedion syndrome) and growth hormone deficiency. Am J Med Genet Part A2004;131:200–3.. Reynart N. Short stature in KBG syndrome: First responses to growth hormone treatment. Horm Res Paediatr2015;83(5):361–4. doi:10.1159/000380908 [Epub: 2015 April 1].

AimsWorldwide incidence of autoimmune disease and especially autoimmune thyroid disease (AITD) in children in increasing. Reversal from severe autoimmune hypothyroidism is a rare occurrence. We report a case of a patient with profound hypothyroidism that returned to a euthyroid state within 13 months.ResultsA 15-year-old girl presented with seven months of excessive tiredness, aches and pains all over the body, low mood and difficulty concentrating. Initial results showed severe primary hypothyroidism, with a TSH >100 mU/L (0.30 4.20 mU/L) and a free T4 of 1.6 pmol/L (12.0–22.0 pmol/L), positive antiTPO antibody at 150 IU/ml (0.00 – 30.00 IU/ml) and negative TSH receptor antibody (TRAbs). The patient was commenced on levothyroxine and 3 months later, the patient was diagnosed with coeliac disease and commenced a gluten free diet. After 9 months of levothyroxine, she presented with pain and soreness in the neck area, excessive perspiration, intermittent heat intolerance and was now hyperthyroid (TSH 0.01 mU/L and free T4 25.9 pmol/L). Levothyroxine was therefore stopped. Off medication, 13 months from her initial presentation, she remains clinically and biochemically euthyroid.DiscussionReversal of mild hypothyroidism has been often noticed in clinical practice. However, reversal of severe profound hypothyroidism is rare, especially in patient with multiple autoimmune involvements. Medications, transient TSH receptor blocking antibodies and iodine containing products have been implicated. An Italian study also found that half of the patients with autoimmune hypothyroidism, who followed a gluten free diet, recovered to a state of euthyroidism. We wonder if gluten free diet played a role in our patient’s recovery from such a profound hypothyroidism. It is important to note, that throughout the course of treatment for hypothyroidism, our patient was not on any other medication and the only major change to her lifestyle was the avoidance of gluten.ConclusionsThis case report demonstrates possibility of spontaneous recovery from severe profound hypothyroidism in children. The mechanism of this is not yet understood and role of gluten free diet cannot be ruled out. Further study into similar cases may allow better insights and understanding of immunoregulation, causation and reversal of immunological phenomenon in AITD.

Children with type 1 diabetes (T1DM) constantly balance carbohydrate intake with insulin dose to achieve normoglycemia. TIDM is challenging especially when it is associated with a metabolic condition which restricts dietary intake or affects blood sugar. We review two cases of T1DM, one associated with Phenylketonuria (PKU) the other with medium-chain acyl-CoA dehydrogenase deficiency (MCADD).Case 1: A 4-year-old boy with classical PKU on a phenylalanine restricted diet presented with T1DM. He was started on basal bolus regime after intensive carbohydrate counting.The dietary plans can be conflicting and challenging. Foods low in phenylalanine such as fruit and sugar eaten without restriction previously, must now be eaten in moderation. Complex carbohydrates such as rice need to be both carbohydrate counted and their phenylalanine levels checked adding to meal time complexity. Hypoglycaemic episodes require additional planning, fast acting carbohydrates are taken without restriction, but longer acting carbohydrates containing wheat flour should be avoided due to high phenylalanine levels.In PKU with TIDM carbohydrate counting is crucial and gives children more flexibility in an otherwise rigid diet. Previous case reports of PKU with TIDM suggest lower phenylalanine post TIDM diagnosis showing good control of both condition is achievable.Case 2: A 17-year-old female was diagnosed with MCADD at 1 year and T1DM at 6 years. Her MCADD meant she was prone to hypoglycaemia, as a build-up of fatty-acid intermediates inhibited gluconeogenesis. Her insulin dose had to be carefully titrated to avoid this, particularly as she could not produce ketones to use as an alternate energy source. This reduction in ketone production lead to false reassurance when the child presented with high sugars. Our patient was prone to hypoglycaemia during infection and other catabolic states for which she required an emergency regime of glucose polymer drinks balanced with insulin intake.In managing a metabolic disorder and TIDM patients are trying to achieve multiple outcomes including euglycaemia, preventing catabolism and in one case low phenylalanine levels. These complex multi disease states put a huge strain on families. Patients need comprehensive individual care plans, intensive structured education, multi-disciplinary team approach with specialist dietitian involvement.