Classic Kallmann syndrome (KS) is due to isolated hypogonadotropic hypogonadism. Most patients have gonadotropin-releasing hormone (GnRH) deficiency, as suggested by their response to pulsatile GnRH therapy. The hypothalamic-pituitary function is otherwise normal in most patients, and hypothalamic-pituitary imaging reveals no space-occupying lesions. By definition, either anosmia or severe hyposmia is present in patients with Kallmann syndrome.

Undescended testis (UDT) is a common abnormality, affecting about 1/20 males at birth. Half of these have delayed testicular descent, with the testis in the scrotum by 10-12 weeks after term. Beyond this spontaneous descent is rare. Current treatment recommendations are that UDT beyond 3 months need surgery between 6-12 months of age. Some children have scrotal testes in infancy but develop UDT later in childhood because the spermatic cord does not elongate with age, leaving the testis behind as the scrotum moves further from the groin. The maldescended testis suffers heat stress when not at the lower scrotal temperature (33 degrees Celsius), interfering with testicular physiology and development of germ cells into spermatogonia. Recent evidence suggests orchidopexy between 6-12 months improves germ cell development, with early reports of improved fertility, but no evidence yet for changes in malignancy prognosis.Hypospadias is also a common abnormality in new-born males, affecting about 1/150 boys. Androgens control masculinization of the genital tubercle into penis between 8-12 weeks’ gestation, with tabularization of the urethra from the perineum to the tip of the glans. If this process is disrupted hypospadias occurs, with a variable proximal urethral meatus, failed ventral preputial development producing a dorsal hood, and discrepancy in the ventral versus dorsal penile length, causing a ventral bend in the penis, known as chordee. Surgery to correct hypospadias is recommended between 6-18 months.

Congenital adrenal hyperplasia (CAH) comprises a group of autosomal recessive defects in enzymes that are responsible for cortisol, aldosterone, and, in very rare cases, androgen synthesis. All forms of CAH are characterized by low levels of cortisol, high levels of ACTH, and adrenal hyperplasia. The exact clinical manifestations depend on the enzyme defect. The most common form of CAH, which is caused by a deficiency of 21β-hydroxylase, presents with hypotension, ambiguous genitalia, and virilization (in the female genotype), and/or precocious puberty (in both males and females). It is further characterized by hyponatremia, hyperkalaemia, and metabolic acidosis. Increased levels of 17-hydroxyprogesterone confirm the diagnosis of 21β-hydroxylase deficiency. Treatment of CAH involves lifelong glucocorticoid replacement therapy. Patients with a 21β-hydroxylase deficiency also require mineralocorticoid replacement with fludrocortisone. Complications of CAH include severe hypoglycaemia, adrenal insufficiency, and/or a failure to thrive.

The patient’s sugar levels typically show the Dawn phenomenon.Dawn phenomenon:This is an early morning rise in blood glucose levels secondary to a rise in hormones that increase blood glucose levels. The question suggests that he is undergoing a pubertal growth spurt, suggesting that an increase in these hormones is what has led to the higher morning glucose levels.Other options:- Inactivity at night-time: It is expected, and insulin dose should be adequate despite inactivity during the night.- Inadequate bedtime insulin: It is possible that this is a contributing factor. However, inadequate background insulin is also likely to result in high blood glucose in the day, which the question does not suggest.- Somogyi effect: There are no features suggestive of nocturnal hypoglycaemia that can cause the Somogyi effect.- Nocturnal glycogenesis: Glycogenesis would result in hypoglycaemia, not hyperglycaemia.

Androgen insensitivity syndrome (AIS), previously referred to as testicular feminization, is an X-linked disorder in which the patients are genotypically male (possessing and X and Y chromosome) and phenotypically female. This disorder is rare, with reported incidences from 1 in 20,000 to 1 in 60,000 live male births, and is the result of a missing gene on the X chromosome that is responsible for the cytoplasmic or nuclear testosterone receptor. In its absence, the gonad, which is a testis, produces normal amounts of testosterone| however, the end tissues are unable to respond due to the deficient receptors leading to the external genitalia developing in a female fashion. Anti-Mullerian hormone, which is produced by the testis, is normal in these patients, leading to regression of the Mullerian duct. Wolffian duct development, which depends on testosterone, does not occur as the ducts lack the receptors. The cumulative effect is a genotypic male with normal external female genitalia (without pubic or axillary hair), no menses, normal breast development, short or absent vagina, no internal sex organs, and the presence of testis. Frequently, these patients have bilateral inguinal hernias in childhood, and their presence should arouse suspicion of the diagnosis.

HbA1c stands for glycated haemoglobin. In patients with haemolytic diseases associated with a shortened RBC survival, HbA1c levels can be unusually low despite controlled diabetes mellitus.These haemolytic diseases can include glucose-6-phosphate dehydrogenase deficiency and sickle cell anaemia.HbA1c:It is a measure of non-enzymatic glycation which occurs due to haemoglobin’s exposure to plasma glucose. As plasma glucose increases so does HbA1c.The level of HbA1c quantitively assesses the control of diabetes mellitus over the last 120 days (as this is the life span of a red blood cell).Haemoglobin type A is separated on cation exchange chromatographyOther subsections include HbA1O, HbA1a, HbA1b.According to the updated NICE recommendations (2015):The target level of HbA1c in children with T1DM is 48 mmol/mol (6.5%) or lower. It is monitored every three months. Better control is associated with fewer long term complications

Klinefelter’s syndrome: The low follicle-stimulating hormone (FSH) and luteinising hormone (LH), together with the low testosterone, suggests a hypogonadotropic hypogonadism. We know that there is no mental retardation, and we are told that physical examination is normal and sense of smell would usually not be tested. Consequently a diagnosis of Kallman’s is suggested. We are not told of a family history of growth delay, thus this is unlikely to be constitutional delay. The thyroid-stimulating hormone (TSH) is normal, making hypothyroidism unlikely and this together with the normal prolactin make hypopituitarism most unlikely.

Hypogonadotropic hypogonadismIn Kallmann syndrome: impaired migration of GnRH cells and defective olfactory bulb → ↓ GnRH in hypothalamus → ↓ FSH and ↓ LH → ↓ testosterone and ↓ oestrogenIn hypothalamic and/or pituitary lesions: ↓ pituitary gonadotropins (↓ FSH and ↓ LH) → ↓ testosterone and ↓ oestrogen

Tanner stage two presents with the following: Downy hair, Breast bud palpable under areola (1st pubertal sign in females).Stage 1 (prepubertal) – elevation of papilla only – no pubic hairStage 2 – breast bud forms – sparse, slightly pigmented hair on labia majoraStage 3 – Breast begins to become elevated, extends beyond areola borders – hair becomes more coarse and curlyStage 4 – increased size and elevation. Areola and papilla form secondary mound – adult like, but sparing medial thighsStage 5 – final size, areola returns but papilla remains projected – hair extends to medial thighs

Precocious puberty is the attainment of normal pubertal biochemical and physical features at an abnormally early age. The age cut-offs commonly used to define precocious puberty are 8 years for females and 9 years for males. Precocious puberty may be central (true) or peripheral (false) based on the aetiology. Central precocious puberty is due to the premature activation of the hypothalamic-pituitary-gonadal axis, which in turn leads to the development of secondary sexual characteristics at an earlier than usual age. The best laboratory investigation to diagnose central precocious puberty is a gonadotropin-releasing hormone stimulation test, which is regarded as the gold standard. It requires the collection of multiple blood samples at different time points to measure FSH and LH levels. If the LH levels increase to >8IU/L after stimulation with GnRH, then the diagnosis of central precocious puberty is confirmed.

Bone age is a valuable tool for determining the skeletal maturation in children. An X-ray of the left hand and wrist or knee is used to calculate bone age, which is then compared with the chronological age of the subject to know if the bone age is advanced or delayed. Certain standardized methods are used to score skeletal maturity, the most common methods are the Tanner-Whitehouse (TW) and Greulich-Pyle (GP) methods. The growth plate comprises a resting zone, a proliferative zone, hypertrophic cartilage zone, calcified cartilage zone, and then the ossification zone. This is the zonal distribution from the epiphysis to the diaphysis. After the closure of growth plates, spinal growth still occurs to some extent, adding up to the final height. The growth plates in boys close at around 17 to 19 years of age, while in girls, they close at around 13 to 15 years.

Anorexia nervosa is an eating disorder defined by restriction of energy intake relative to requirements, leading to a significantly low body weight. Patients will have an intense fear of gaining weight and distorted body image with the inability to recognize the seriousness of their significantly low body weight. Athletes in sports such as ballet, long-distance running, and martial arts are pressured to maintain lean body weights to outperform the competition.

Hormones can be secreted in a number of different ways, thus plasma levels of each may vary throughout the day. Many of these exhibit intermittent secretion related to sleep (growth hormone, and prolactin), while others are released based on circadian rhythms (cortisol). Some are released in a pulsatile fashion throughout the day such as FSH, LH, Thyroxine, while others are stress related like cortisol.

Fragile X syndrome is a genetic condition that causes a range of developmental problems including learning disabilities and cognitive impairment. Usually, males are more severely affected by this disorder than females.Affected individuals usually have delayed development of speech and language by age 2. Most males with fragile X syndrome have mild to moderate intellectual disability, while about one-third of affected females are intellectually disabled. Children with fragile X syndrome may also have anxiety and hyperactive behaviour such as fidgeting or impulsive actions. They may have attention deficit disorder (ADD), which includes an impaired ability to maintain attention and difficulty focusing on specific tasks. About one-third of individuals with fragile X syndrome have features of autism spectrum disorder that affect communication and social interaction. Seizures occur in about 15 percent of males and about 5 percent of females with fragile X syndrome.Most males and about half of females with fragile X syndrome have characteristic physical features that become more apparent with age. These features include a long and narrow face, large ears, a prominent jaw and forehead, unusually flexible fingers, flat feet, and in males, enlarged testicles (macroorchidism) after puberty.

HLA-DR (3 and 4) have been associated with an increased risk for idiopathic diabetes mellitus.Type 1 diabetes has a high heritability compared to type 2Identical twins have a 30-50% risk if their twin has type 1 diabetes

Somogyi effect presents with night-time hypoglycaemia followed by early-morning hyperglycaemia, hence the glycosuria.

The following methods are adopted for the treatment of DKA:

– Fluids: Bolus of 10 ml/kg of normal saline. Stop at three boluses to avoid precipitating cerebral oedema. The remaining deficit has to be corrected over 48 hours. Strict input/output, U&E, and pH monitoring is necessary in such patients.

– Insulin: Insulin infusion can be initiated at 0.05-0.1 unit/kg/hour. It is essential to monitor blood glucose closely, and the aim is to decrease by 2 mmol/hour.

– Potassium: Initially, it will be high, but following insulin administration, the levels drop quickly as K+ enters cells with glucose, and thus, replacement is almost always necessary.

– Acidosis: Bicarbonate is avoided unless pH is less than 7. Acidosis will get corrected with the correction of fluid and insulin deficits. The definitive treatment is directed towards correcting the underlying precipitants of DKA, e.g. sepsis, infections.

Puberty is when a child’s body begins to develop and change as they become an adult.The average age for girls to begin puberty is 11, while for boys the average age is 12.It’s completely normal for puberty to begin at any point from the ages of 8 to 14. The process can take up to 4 years.

Adrenal insufficiency is a serious medical condition that leads to inadequate secretion of corticosteroids. There are three main types of adrenal insufficiency: primary, secondary, and tertiary, based on the location of the abnormality. Primary adrenal insufficiency is caused by any pathology located inside the adrenal glands. The most common cause of primary adrenal insufficiency is Addison’s disease, which is an autoimmune condition. Adrenoleukodystrophy is an X-linked neurodegenerative disease that also causes primary adrenal insufficiency. Secondary adrenal insufficiency is caused by any pathological impairment of the pituitary gland or the hypothalamus. The important causes of secondary adrenal insufficiency include iatrogenic (steroid use), pituitary tumours like craniopharyngioma, and conditions leading to panhypopituitarism like Sheehan’s syndrome. Tertiary adrenal insufficiency is caused by the deficiency of the corticotropin-releasing hormone. Hypoparathyroidism does not cause adrenal insufficiency.

Hypercalcemia refers to increased serum calcium levels and is characterized by a number of significant constellations, including polyuria, muscle weakness, abdominal pain, fatigue, and cardiac arrhythmias. The causes of hypercalcemia can be classified as PTH-dependant causes and PTH-independent causes. The causes can be both congenital and acquired. The most common cause of PTH-dependent hypercalcemia is the primary or tertiary hyperparathyroidism, resulting from parathyroid gland tumours. Hyperparathyroidism is also associated with chronic renal failure. PTH-independent hypercalcemia is caused by William’s syndrome, hypervitaminosis (vitamin A and D intoxication), endocrinopathies (hyperthyroidism), various drugs (thiazide diuretics), and some inborn errors of metabolism. One of the congenital causes of PTH-independent hypercalcemia is idiopathic infantile hypercalcemia.

A bone age study helps doctors estimate the maturity of a child’s skeletal system. It’s usually done by taking a single X-ray of the left wrist, hand, and fingers. It is a safe and painless procedure that uses a small amount of radiation. The bones on the X-ray image are compared with X-rays images in a standard atlas of bone development, which is based on data from large numbers of other kids of the same gender and age. The bone age is measured in years.

Precocious puberty refers to the appearance of physical and hormonal signs of pubertal development at an earlier age than is considered normal.Most patients, particularly girls suspected of having central precocious puberty, are otherwise healthy children whose pubertal maturation begins at the early end of the normal distribution curveIn a series of more than 200 patients evaluated at a single medical centre, central precocious puberty occurred 5 times more often in girls than boys.GnRH-dependent precocious puberty is treated with GnRH agonists or Luteinizing Hormone Releasing Hormone (LHRH). Follow up every 4-6 months to ensure that progression of puberty has been arrestedFavourable signs include normalization of accelerated growth, reduction (or at least no increase) in size of breasts, and suppression of gonadotropin levels after a challenge of GnRHThe ideal testing frequency has not been established. Monitor bone age yearly to confirm that the rapid advancement seen in the untreated state has slowed, typically to a half year of bone age per year or less

WHO states that diabetes can be diagnosed from a single fasting glucose of > 7.0 mmol/l with characteristic symptoms or a glucose level of > 11.1 mmol/l 2 hours after a glucose load. Two fasting glucose levels of > 7.0 mmol/l on separate occasions can also fit the diagnosis in the absence of characteristic symptoms.

A low serum free T4 level with a low, or normal serum TSH level would indicate secondary hypothyroidism. A normal TSH response to TRH is a rise at 20 minutes post-dose and then a fall by 60 minutes, while a normal prolactin response would be a rise at 20 minutes and then a fall by 60 minutes. A continued rise of TSH at 60 minutes implies hypothalamic damage. Secondary hypothyroidism is indicated by a low baseline TSH level, while primary hypothyroidism is demonstrated by a raised TSH.

Graves disease is an autoimmune disorder in which patients present with thyrotoxicosis and related ophthalmopathy, and dermopathy. Many affected patients experience hyperthyroidism. Peak incidence of graves disease is after the 3rd decade of life and is more common in women than in men. Graves susceptibility is association with HLA-DR3. Clinical features of Graves disease include an increased metabolic rate, heat intolerance, irritability, weight loss despite increasing appetite, diarrhoea palpitations, chemosis, acropachy and onycholysis.

Precocious puberty is the attainment of normal pubertal biochemical and physical features at an abnormally earlier age. The age cut-offs commonly used to define precocious puberty are 8 years for females and 9 years for males. The onset of normal puberty is triggered by gonadotropic-releasing hormones from the hypothalamus.In most of the familial cases, the condition is transmitted by affected father. In boys, this makes up about 5% of the cases.Full adult height potential is not achieved in patients of precious puberty, although there is an advanced bone maturation.

The boy presented with mild hypoglycaemia and should be managed at home with fast-acting carbs. He should not sleep immediately. His parents should monitor his blood glucose every hour without letting him sleep in between.

Congenital hypothyroidism is associated with failure to thrive, macroglossia, prolonged jaundice of a new-born and constipation.

Craniopharyngiomas (also known as Rathke pouch tumours, adamantinomas or hypophyseal duct tumours) affect children mainly between the age of 5 and 10 years. It constitutes 9% of brain tumours affecting the paediatric population. These are slow-growing tumours which can also be cystic, and arise from the pituitary stalk, specifically the nests of epithelium derived from Rathke’s pouch. Histologically, this tumour shows nests of squamous epithelium which is lined on the outside by radially arranged cells. Calcium deposition is often seen with a papillary type of architecture.
ACTH-secreting pituitary adenomas are rare and mostly microadenomas. Paediatric astrocytoma’s usually occur in the posterior fossa. Although null cell adenomas can cause mass effect and give rise to the described symptoms, they are not suprasellar. Prolactinomas can also show symptoms of headache and disturbances in the visual field, however they are known to be small and slow-growing.

Diabetes ketoacidosis is one of the most serious and acute complications of diabetes. At the time of presentation and during treatment of diabetic ketoacidosis (DKA), several metabolic and electrolyte derangements can ultimately result in respiratory compromise. Most commonly, hypokalaemia, hypomagnesemia and hypophosphatemia can eventually lead to respiratory muscles failure. Furthermore, tachypnoea, hyperpnea and more severely, Kussmaul breathing pattern can develop. Also, hydrostatic and non-hydrostatic pulmonary oedema can occur secondary to volume shifts into the extracellular space and secondary to increased permeability of the pulmonary capillaries. The presence of respiratory failure in patients with DKA is associated with higher morbidity and mortality. Being familiar with the causes of respiratory compromise in DKA, and how to treat them, may represent better outcomes for patients with DKA.