Cases of neonatal infant ambiguous genitalia can be a great source of psychological stress for families. One of the most important next steps in managing the case is reassuring the parents that the best care will be given to the baby and then informing them about the investigations that will need to be performed before a sex can be assigned. The sex should not be guessed just by examination nor assigned by karyotyping. Thorough investigations must be completed with the help of endocrinologists for the best outcome.

The adult height potential may be calculated for a male child by (father’s height in cm + mother’s height in cm) / 2 then add 7 cm.In the scenario provided: (170 + 150)/2 + 7 = 167 cm = 1.67 m.For a female child by (father’s height in cm + mother’s height in cm) / 2 then minus 7 cm.This can then be plotted on a height centile chart to find the mid-parental centile.Causes of short stature include:- Normal variant (often familial)- Constitutional delay of growth and puberty- Chronic illness, e.g. cystic fibrosis, inflammatory bowel disease- Endocrine: growth hormone deficiency, hypothyroidism, steroid excess syndromes: Turner’s, Down’s, Prader-Willi- Skeletal dysplasias, e.g. achondroplasia

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.

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

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.

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.

Deficiency of 21-hydroxylase, resulting from mutations or deletions of CYP21A, is the most common form of Congenital Adrenal Hyperplasia, accounting for more than 90% of cases.Females with mild 21-hydroxylase deficiency are identified later in childhood because of precocious pubic hair, clitoromegaly, or both, often accompanied by accelerated growth and skeletal maturation (simple virilizing adrenal hyperplasia)Diagnosis of 21-hydroxylase deficiency: High serum concentration of 17-hydroxyprogesterone (usually >1000 ng/dL) and urinary pregnanetriol (metabolite of 17-hydroxyprogesterone) in the presence of clinical features suggestive of the disease| 24-hour urinary 17-ketosteroid levels are elevated

The main cause of growth hormone (GH) deficiency is a pituitary tumour or the consequences of treatment of the tumour including surgery and/or radiation therapy.Sheehan’s syndrome (SS) is postpartum hypopituitarism caused by necrosis of the pituitary gland. It is usually the result of severe hypotension or shock caused by massive haemorrhage during or after delivery. Patients with SS have varying degrees of anterior pituitary hormone deficiency.Laron syndrome is Insulin-like growth factor I (IGF-I) deficiency due to GH resistance or insensitivity due to genetic disorders of the GH receptor causing GH receptor deficiency.

Individuals with Marfan syndrome are usually tall and slender, have elongated fingers and toes (arachnodactyly), loose joints, and have an arm span that exceeds their body height. Other common features include a long and narrow face, crowded teeth, an abnormal curvature of the spine (scoliosis or kyphosis), stretch marks (striae) not related to weight gain or loss, and either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum). Some individuals develop an abnormal accumulation of air in the chest cavity that can result in the collapse of a lung (spontaneous pneumothorax). A membrane called the dura, which surrounds the brain and spinal cord, can be abnormally enlarged (dural ectasia) in people with Marfan syndrome. Dural ectasia can cause pain in the back, abdomen, legs, or head. Most individuals with Marfan syndrome have some degree of near-sightedness (myopia). Clouding of the lens (cataract) may occur in mid-adulthood, and increased pressure within the eye (glaucoma) occurs more frequently in people with Marfan syndrome than in those without the condition.

Three physical changes – breast budding, pubic hair growth, and axillary hair growth in the order mentioned precede menarche. These changes are due to oestrogen, a hormone essential for pubertal development.The various pubertal changes in males include:-Testicular growth: It is the first sign of puberty occurring at around 12 years of age (Range = 10 – 15 years).- Testicular volume: An increase in the volume of testicles to 4 ml indicates the onset of pubertyThe various pubertal changes in females include:- The first sign is breast development at around 11.5 years of age (range = 9-13 years)- Followed by the onset of height spurt reaching the maximum in puberty (at 12 years of age)- The final change that occurs is termed menarche at 13 (11-15) years of age.Some of the other pubertal changes include:- Gynecomastia may develop in boys- Asymmetrical breast growth may occur in girls- Diffuse enlargement of the thyroid gland

A height that is above the 97th percentile for age and sex is described as a tall stature. The most common cause of tall stature is constitutional or familial, followed by nutritional causes. Hormonal causes of tall stature include hyperthyroidism, growth hormone excess, and precocious puberty. Some important chromosomal and syndromic causes of tall stature are Klinefelter’s syndrome, homocystinuria, Marfan’s syndrome, Sotos syndrome, Beckwith-Weidman syndrome, and Weaver syndrome. Laurence-Moon syndrome is an autosomal recessive disorder characterized by short stature, retinitis pigmentosa, and spastic paraplegia.

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.

The hypothalamus and pituitary gland control how much testosterone the testes produce and secrete. The hypothalamus sends a signal to the pituitary gland to release gonadotrophic substances (follicle stimulating hormone and luteinizing hormone). Luteinizing hormone (LH) stimulates testosterone production.

In this case scenario, the pH is too low to be fully explained by a respiratory acidosis. Usually, if there is a metabolic acidosis, the respiratory system will try to compensate by hyperventilation and reduced pCO2. In this case, however, the pCO2 is raised suggesting the presence of a respiratory component.Therefore, this boy has mixed metabolic and respiratory acidosis, most probably due to severe exacerbation of this asthma, which led to diabetic ketoacidosis.Note:Normal values:pH: 7.35 – 7.45pO2: 10 – 14 kPapCO2: 4.5 – 6 kPaBase excess (BE): -2 – 2 mmol/LHCO3: 22 – 26 mmol/L

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.

The boy had a renal transplant, for which he needs immune suppression. For the exogenous immune suppression an exogenous steroid is needed, which in this case is responsible for the primary Cushing syndrome manifesting with short stature. The administration of steroids before the physiological fusion of the growth plate can lead to premature fusion with permanent cessation of bone growth.

The child has experienced the Somogyi phenomenon. It is a phenomenon where there’s a morning rise in blood sugar. Often it occurs as posthypoglycemic hyperglycaemia and follows nocturnal hypoglycaemia. The mechanism is the production of counter-regulatory hormones like glucagon, cortisol and adrenaline, which increase glucose. She can be managed by reducing her evening insulin dosage and increasing complex carbohydrates for supper (evening meal).Type I diabetes mellitus:It is a chronic illness that is characterised by the inability to produce insulin. It is caused by autoimmune destruction of the beta cells in the pancreas and often presents with ketoacidosis.The patient can present with symptoms suggestive of polyuria, polydipsia, and weight loss. There can be periods of islet cell regeneration in these patients, which leads to a ‘honeymoon period’ of remission.Symptoms occur when there is < 20% of islet cell activity left.Insulin therapy is required in almost all children with type 1 diabetes.Most children require multiple insulin injections throughout the day via subcutaneous insulin pumps.Target HbA1c in these patients is 48 mmol/mol according to the updated NICE guidelines.

Bone age is used to determine the maturation of a child’s bones’ and is used to detect pathological growth. This is done using the X-ray of the wrist. Several conditions can either advance or delay the bone age such that they may not match the child’s chronological age. Bone age is advanced in conditions where there are prolonged or elevated sex hormone levels such as precocious puberty, or in genetic overgrowth conditions such as Beckwith-Wiedemann syndrome. Bone age is delayed in constitutional growth delay, chronic ill health, endocrine disorders such as growth hormone deficiencies or hypothyroidism, genetic disorders such as Trisomy 21, Trisomy 18, and Turner’s syndrome. Obesity is unlikely to cause growth delay.

This child has pseudo hypoparathyroidism. It is a heterogeneous group of rare endocrine disorders characterized by normal renal function and resistance to the action of parathyroid hormone (PTH), manifesting with hypocalcaemia, hyperphosphatemia, and increased serum concentration of PTH.Patients with pseudo hypoparathyroidism type 1a present with a characteristic phenotype collectively called Albright hereditary osteodystrophy (AHO). The constellation of findings includes the following:Short statureStocky habitusObesityDevelopmental delayRound faceDental hypoplasiaBrachymetacarpalsBrachymetatarsalsSoft tissue calcification/ossificationThe goals of therapy are to maintain serum total and ionized calcium levels within the reference range to avoid hypercalcaemia and to suppress PTH levels to normal. This is important because elevated PTH levels in patients with PHP can cause increased bone remodelling and lead to hyper-parathyroid bone disease.The goals of pharmacotherapy are to correct calcium deficiency, to prevent complications, and to reduce morbidity. Intravenous calcium is the initial treatment for all patients with severe symptomatic hypocalcaemia. Administration of oral calcium and 1alpha-hydroxylated vitamin D metabolites, such as calcitriol, remains the mainstay of treatment and should be initiated in every patient with a diagnosis of pseudo hypoparathyroidism.

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.

Precocious Puberty is the development of secondary sexual characteristics before the age of 8 in females, and 9 in males. The first sign of early puberty in males is testicular enlargement, followed by growth of the penis and the scrotum at least a year after. Precocious puberty in boys in uncommon and usually has an organic cause leading to excess secretion of testosterone. These can be gonadotrophin dependent in the case of an inter cranial lesion, where the testes would be bilaterally enlarged, or from excess production from the adrenal gland in the case of adrenal hyperplasia or a tumour.

Intensive physical training and participation in competitive sports during childhood and early adolescence may affect athletes’ pubertal development.Female athletes who do not begin secondary sexual development by the age of 14 or menstruation by the age of 16 warrant a comprehensive evaluation and treatment.Since she is still 14, adequate diet and observation are enough.

Mild deficiencies of 21-hydroxylase or 3-beta-hydroxysteroid dehydrogenase activity may present in adolescence or adulthood with oligomenorrhea, hirsutism, and/or infertility. This is termed nonclassical adrenal hyperplasia.Late-onset or nonclassical congenital adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders. Reported prevalence ranges from 1 in 30 to 1 in 1000. Affected individuals typically present due to signs and symptoms of androgen excess. Treatment needs to be directed toward the symptoms. Goals of treatment include normal linear growth velocity, a normal rate of skeletal maturation, ‘on-time’ puberty, regular menstrual cycles, prevention of or limited progression of hirsutism and acne, and fertility. Treatment needs to be individualized and should not be initiated merely to decrease abnormally elevated hormone concentrations.Normal Ultrasound rules out Turner’s syndrome.

Androgen excess is one of the most common causes of advanced bone age. It usually occurs in precocious puberty or congenital adrenal hyperplasia.

Zona fasciculata of the adrenal produces the maximum levels of cortisol in the body.Functions of cortisol:- Increases blood pressure: permits normal response to angiotensin II and catecholamines by up-regulating alpha-1 receptors on arterioles.- Inhibits bone formation: decreases osteoblasts, type 1 collagen and absorption of calcium from the gut, and increases osteoclastic activity.- Increases insulin resistance.- Increases gluconeogenesis, lipolysis and proteolysis.- Inhibits inflammatory and immune responses.- Maintains function of skeletal and cardiac muscle.An excess of corticosteroids in the body causes various symptoms that are a part of Cushing’s syndrome.

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

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

Retinopathy screening need not be done on an annual basis for a 9-year-old child. Screening for diabetic retinopathy should begin at the age of 12.Diabetes mellitus is an increasing problem in both developing and developed countries alike. Some of the risk factors include:ObesityFamily historyFemale sex Asian and African racesPresence of acanthosis nigricans is seen with type 2 but not type 1 diabetesThe diagnosis is mostly incidental or subacute.The treatment aims are good blood sugar control, maintenance of normal BMI, and reduction of complications. The treatment modality also includes lifestyle modifications and cessation of smoking. Even after all this, diabetic ketoacidosis can still occur.Management of diabetes mellitus – NICE guidelines (Updated, 2015): – Standard release metformin should be offered from the moment of diagnosis.- HBA1c should be measured every three months. The target HBA1c level of 48 mmol/mol (6.5%) or lower is ideal for minimising the risk of long term complications.- Children should undergo an eye examination by an optician every two years.- Annual immunisation against influenza and pneumococcal infections are essential.- There is an increased risk of psychological and psychosocial difficulties if the child with type 1 diabetes is on insulin or oral hypoglycaemic medications. These include anxiety disorder, depression, behavioural and conduct disorders and family conflict.- Annual monitoring to be done for:Hypertension starting at diagnosis.Dyslipidaemia starting at diagnosis.Screening for microalbuminuria starting at diagnosis.Diabetic retinopathy from 12 years of age.

While the clinical scenario and the anosmic presentation of the child are highly suggestive of Kallmann’s syndrome, reduced testosterone, FSH and LH levels can confirm the diagnosis.Kallman’s syndrome is a recognised cause of delayed puberty secondary to hypogonadotropic hypogonadism. It is usually inherited as an X-linked recessive trait. Kallman’s syndrome is thought to be caused by a failure of GnRH-secreting neurons to migrate to the hypothalamus.Clinical features of Kallmann’s syndrome include:- Delayed puberty- Hypogonadism, cryptorchidism- Anosmia- Low sex hormone levels – Inappropriately low/normal LH and FSH levels- Some patients can present with associated cleft lip/palate and visual/hearing defects.

Insertion sites and sensor sites should be rotated each time the infusion set or glucose sensor is changed. This keeps the tissue healthy and allows previous sites to completely heal before reusing them. Change infusion set every 2 to 3 days to help prevent infection.

Many factors are related with the stimulation of bone formation and growth, the pubertal growth spurt, epiphyseal senescence, and fusion, including nutritional, cellular, paracrine, and endocrine factors. An important cellular factor in these processes is the differentiation and aging of chondrocytes in the growth plate. Important paracrine factors include the many molecular pathways involved in chondrocyte differentiation, vascularization, and ossification. Oestrogen and the GH-IGF-I axis are important endocrine factors.

Turners syndrome is a chromosomal syndrome affecting the development of females. In this condition, all or part of the X chromosome gets deleted, producing the Karyotype 45 XO or 45XO/46XX. Spontaneous foetal loss is common in the first trimester, but foetuses which survive are born small for date, and may have lymphedema, and poor feeding in the neonatal period. These patients face numerous medical and developmental problems throughout their lifetimes including growth and puberty failure due to premature ovarian failure/ hypergonadotropic hypogonadism. However spontaneous puberty can be seen in up to 20% of females with Turner’s syndrome.

The European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine Rotterdam consensus (ESHRE/ASRM) developed and enlarged the diagnosis of PCOS, requiring two of three features: anovulation or oligo-ovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology (PCOM) seen on ultrasound. Finally the Androgen Excess Society defined PCOS as hyperandrogenism with ovarian dysfunction or polycystic ovaries

Lypohypertrophy is the most common skin-related complication of insulin injection.

Addison disease is adrenocortical insufficiency due to the destruction or dysfunction of the entire adrenal cortex. It affects glucocorticoid and mineralocorticoid function. The onset of disease usually occurs when 90% or more of both adrenal cortices are dysfunctional. The most common symptoms are fatigue, muscle weakness, loss of appetite, weight loss, and abdominal pain. Adrenal insufficiency can be caused by autoimmune disease or suddenly stopping steroid medicines used to treat other conditions, among other causes.

The average age for girls to begin puberty is 11.The first sign of puberty in girls is usually that their breasts begin to develop.It’s normal for breast buds to sometimes be very tender or for one breast to start to develop several months before the other one.Pubic hair also starts to grow, and some girls may notice more hair on their legs and arms.After a year or so of puberty beginning, and for the next couple of years:girls’ breasts continue to grow and become fuller.Around 2 years after beginning puberty, girls usually have their first period,pubic hair becomes coarser and curlierunderarm hair begins to grow. From the time their periods start, girls grow 5 to 7.5cm (2 to 3 inches) annually over the next year or two, then reach their adult height.After about 4 years of puberty in girls:breasts become adult-likepubic hair has spread to the inner thighgenitals should now be fully developedgirls stop growing taller.

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.

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.

The most probable diagnosis for this boy is primary hypothyroidism.Rationale:The development of secondary sexual characteristics in a boy aged less than 9 years of age is highly suggestive of precocious puberty.Around 80% of boys with precocious puberty have pathological causes and require detailed investigation. In this case, the child has long-standing short stature but coupled with the early puberty and delay in bone age, the diagnosis is primary hypothyroidism, which is the only cause of this clinical picture.

The thyroid gland is one of the first endocrine glands to develop, and is formed from the endoderm of the epithelial tissue of the primitive pharynx. The mature gland is functionally made up of follicles with colloid which contain the pro hormone thyroglobulin. Thyroid hormone is synthesised at a cellular level and is stored as thyroglobulin, before its release as thyroid hormone, a major modulator of metabolism. In between the follicular cells are parafollicular, or C-cells which secrete parathyroid hormone or calcitonin which are responsible for calcium regulation in the body.

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.

Congenital hypothyroidism is one of the most important diseases of the new-born, which may lead to mental and physical retardation when treatment is delayed or an appropriate dosage of thyroxine is not administered. The most alarming and earliest sign is jaundice, especially when it is prolonged, during the neonatal period.

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.

This girl most probably has Turner’s syndrome, which is caused by the absence of one set of genes from the short arm of one X chromosome.Turner syndrome is a lifelong condition and needs lifelong oestrogen replacement therapy. Oestrogen is usually started at age 12-15 years. Treatment can be started with continuous low-dose oestrogens. These can be cycled in a 3-weeks on, 1-week off regimen after 6-18 months| progestin can be added later.In childhood, growth hormone therapy is standard to prevent short stature as an adult.Fetal ovarian development seems to be normal in Turner syndrome, with degeneration occurring in most cases around the time of birth so pulsatile GnRH and luteinising hormone would be of no use.

Adrenal insufficiency is a serious medical condition that leads to inadequate secretion of corticosteroids. The consequences of this deficiency are numerous electrolyte and acid-base imbalances, which include hyponatremia, hyperkalaemia, hypercalcemia, hypoglycaemia, metabolic alkalosis, and dehydration.

McCune–Albright syndrome, characterised by polyostotic fibrous dysplasia, café au lait spots, sexual precocity, and hyperfunction of multiple endocrine glands, is the result of G-protein abnormality.

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.

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.

Diabetes insipidus (DI) is defined as the passage of large volumes (>3 L/24 hr) of dilute urine (< 300 mOsm/kg). It has the following 2 major forms:Central (neurogenic, pituitary, or neurohypophyseal) DI, characterized by decreased secretion of antidiuretic hormone (ADH| also referred to as arginine vasopressin [AVP])Nephrogenic DI, characterized by decreased ability to concentrate urine because of resistance to ADH action in the kidney.The boy most probably has nephrogenic diabetes insidious (DI) not central DI so he is not responding to the ADH treatment.

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.