Endocrine Disorders in Children PDF

# Endocrine disorders in children - by Dr:Dalia Hassan ## **The Endocrine System** - Pineal Gland - Hypothalamus - Pituitary Gland - Thyroid Gland - Parathyroid Glands - Thymus - Adrenal Glands _(atop kidneys)_ - Pancreas - Ovary _(female)_ - Testis _(male)_ ## **Hypothalamic-Pituitary System**...

# Endocrine disorders in children - by Dr:Dalia Hassan ## **The Endocrine System** - Pineal Gland - Hypothalamus - Pituitary Gland - Thyroid Gland - Parathyroid Glands - Thymus - Adrenal Glands _(atop kidneys)_ - Pancreas - Ovary _(female)_ - Testis _(male)_ ## **Hypothalamic-Pituitary System** - The pituitary gland is a midline structure situated inferior to the hypothalamus within the pituitary fossa. It consists of three lobes: the anterior and posterior lobes with a small intervening intermediate lobe. The anterior and intermediate lobes are derived from the buccal mucosa whereas the posterior lobe is derived from neural ectoderm. The anterior pituitary has five neuroendocrine cell types each defined by the hormone they produce: - Corticotrophs _(ACTH)_ - Somatotrophs _(GH)_ - Gonadotrophs _(LH, FSH)_ - Thyrotrophs _(thyroid-stimulating hormone or TSH)_ - Lactotrophs _(prolactin or PRL)_ - The posterior pituitary secretes oxytocin and antidiuretic hormone. ## **Pituitary Disorders** ### **Congenital** - Agenesis of the corpus callosum - Structural abnormalities: - Septo-optic dysplasia - Pituitary hypoplasia - Idiopathic hormonal abnormalities: - Isolated GH deficiency - Idiopathic precocious puberty ### **Acquired** #### **Excess** - Intracranial tumours - Cushing disease - pituitary adenoma #### **Deficiency** *(e.g. secondary to treatment with radiation or surgery)* - Pituitary damage - Tumours - Surgery - Radiotherapy - Trauma ## **Posterior Pituitary Disorder** ## **Syndrome of inappropriate ADH secretion (SIADH)** - by high levels of ADH in the absence of normal physiologic stimuli for its release - water retention → ↑ total body H₂O → ↓ aldosterone production - solute loss (Na+) → hyponatremia → hypo osmolality suppression of renin production - ↓ aldosterone production → ↓ Na+ reabsorption in kidney - rapid decrease of serum Na+ from 140 to 130 mmol/l → thirst, anorexia, dyspnoea on exertion, fatigue occur ## **Diabetes insipidus (DI)** - is related to an insufficiency of ADH leading to polyuria and polydipsia. ### **Types of DI** - **Neurogenic or central form** - ↓ amount of ADH production - **Nephrogenic form** - inadequate response to ADH. - increase in plasma osmolality → thirst → polydipsia. - ↑ urine output, ↓ urine specific gravity *(1.00-1.005)* - dehydration *(if not adequate fluid intake)* ## **Diseases of the anterior pituitary gland** - they depend on the affected hormones if all hormones are deficient → panhypopituitarism - ACTH deficiency → *(within 2 weeks)* symptoms of cortisol insufficiency are developed: - nausea, vomiting, anorexia, fatigue, weakness - hypoglycaemia *(it is caused by increased sensitivity of tissues to insulin, decreased glycogen reserves, decreased gluconeogenesis)* - in adult female, loss of body hair and decreased libido → due to decreased adrenal androgen production - limited maximum aldosterone secretion **These are depicted in a diagram on page 14 showing the effects of mild, moderate and severe anterior pituitary deficiency.** ## **Anterior Pituitary** - Short stature - Pubertal delay or arrest - Precocious puberty - Thyroid tumours - Infertility - Hypopituitarism - isolated or multiple - Gynaecomastia ## **TSH deficiency** - *(within 4-8 weeks)* symptoms of TSH deficiency are developed: - cold intolerance - dryness of skin - mild myxoedema - lethargy - Precocious puberty ## **FSH and LH deficiencies** - In reproductive age.: - Delayed puberty, amenorrhea. - atrophic changes of vagina, uterus and breasts *(in female)*. - Testicular atrophy in *(males)*. ## **Hyperpituitarism** - Excess hormone production from an adenoma e.g. prolactinoma *(prolactin)* or acromegaly *(growth hormone)* is much less common than in adulthood. ## **Adrenal Disorders** - **Congenital adrenal hyperplasia (CAH)** is the most common non-iatrogenic cause of insufficient cortisol and mineralocorticoid secretion. - **Presentation is with:** About 70% to 80% are also unable to produce aldosterone, leading to salt loss *(low sodium and high potassium)*: - virilisation of the external genitalia in female infants, with clitoral hypertrophy and variable fusion of the labia - in the infant male, the penis may be enlarged and the scrotum pigmented. ## **Diagnosis** - This is made by finding markedly raised levels of the metabolic precursor 17a-hydroxy-progesterone in the blood. - In slat losers, the biochemical abnormalities are: - low plasma sodium - high plasma potassium - metabolic acidosis - hypoglycemia ## **Treatment** - Infants with a salt-losing crisis require sodium chloride, glucose, and hydrocortisone intravenously. - lifelong glucocorticoids - monitoring of growth, skeletal maturity, and plasma androgens and 17a-hydroxy progesterone. - Affected females will sometimes require corrective surgery to their external genitalia within the first year. - Definitive surgical reconstruction is usually delayed until late puberty. ## **Death** - can occur from adrenal crisis at the time of illness. ## **Primary adrenal insufficiency (Addison disease)** - This is rare in childhood and may result from: - an autoimmune process, sometimes in association with other autoimmune endocrine disorders, e.g. diabetes mellitus, hypothyroidism, hypoparathyroidism - hemorrhage/infarction - neonatal, meningococcal septicemia - X-linked adrenoleucodystrophy, a rare neurodegenerative metabolic disorder - tuberculosis, now rare. - Adrenal insufficiency may also be secondary to pituitary dysfunction from hypothalamic-pituitary disease or from hypothalamic-pituitary-adrenal suppression following long-term corticosteroid therapy. ## **Presentation** - Infants present acutely with a salt-losing crisis, hypotension and/or hypoglycemia. Dehydration may follow a gastroenteritis-like illness, from which the child recovers until the next episode. - In older children, presentation is usually with nonspecific symptoms, such as fatigue, and pigmentation. - Postural hypotension can be a clue: check lying and standing blood pressure ## **Addison's Disease Symptoms** - Fatigue and Lethargy - Low Mood or Irritability - Weight loss - Muscle Weakness ## **Diagnosis** - This is made by finding hyponatraemia and hyperkalaemia, often associated with a metabolic acidosis and hypoglycaemia. - The plasma cortisol is low and the plasma ACTH concentration high *(except in pituitary dysfunction)*. With an ACTH *(Synacthen)* test, plasma cortisol concentrations remain low in both primary adrenal dysfunction. ## **Management** - An adrenal crisis requires urgent treatment with intravenous saline, glucose and hydrocortisone. - Long-term treatment is with glucocorticoid and mineralocorticoid replacement. - The dose of glucocorticoid needs to be increased by three times at times of illness or for an operation. - Parents are taught how to inject intramuscular hydrocortisone in an emergency. - Patient may wear bracelet or having card. ## **Cushing Syndrome** - Glucocorticoid excess in children is usually a side-effect of long-term glucocorticoid treatment *(intravenous, oral or, more rarely, inhaled, nasal, or topical)* for conditions such as nephrotic syndrome or asthma. - Other causes of glucocorticoid excess are rare. - It may be ACTH-driven, from a pituitary adenoma, usually in older children, or from ectopic ACTH producing tumours very rare. ## **Clinical Features of Cushing Syndrome** - Growth failure/short stature - Face and trunk obesity - Red cheeks - Hirsutism - Striae - Hypertension - Bruising - Carbohydrate intolerance - Muscle wasting and weakness - Osteopenia - Psychological problems. **This is depicted in a diagram on page 29, depicting a person with Cushing's Disease or Syndrome Symptoms.** ## **Diagnosis** - diurnal variation of cortisol *(high in the morning, low at midnight)* may be shown to be lost - in Cushing syndrome the midnight concentration is also high. - The 24-hour urine free cortisol is also high. After the administration of dexamethasone at night time, there is failure to suppress the plasma 09.00 hour cortisol levels the following morning. - CT OR MRI to identify tumor. ## **Treatment** - Adrenal tumours are usually unilateral and are treated by adrenalectomy and radiotherapy if indicated. - Pituitary adenomas releasing ACTH *(Cushing disease)* are best treated by transsphenoidal resection. - Radiotherapy can be used. ## **Hyperparathyroidism** - In neonates and young children, it is associated with some rare genetic abnormalities *(e.g. William syndrome)*, but in later childhood can be secondary to adenomas occurring spontaneously or as part of the multiple endocrine neoplasia syndromes. ## **Presentation** - high calcium level, causing constipation, anorexia, lethargy and behavioral effects, polyuria, and polydipsia. - Bony erosions of the phalanges may be seen on a hand radiograph. ## **Treatment** - Severe hypercalcaemia is treated with rehydration, diuretics, and bisphosphonates. ## **Hypoparathyroidism** - hypoparathyroidism, which is rare in childhood, in addition to a low serum calcium, there is a raised serum phosphate and a normal alkaline phosphatase. - The parathyroid hormone level is very low. - In infants is usually due to a congenital deficiency *(DiGeorge syndrome)*, associated with thymic aplasia, defective immunity, cardiac defects, and facial abnormalities. - In older children, hypoparathyroidism is usually an autoimmune disorder and can be associated with Addison disease. ## **Presentation** - Severe hypocalcaemia leads to muscle spasm, fits, stridor, and diarrhoea. - **pseudohypoparathyroidism** there is end-organ resistance to the action of parathyroid hormone caused by a mutation in a signaling molecule Hypocalcaemia may also result in rickets. - Associated abnormalities are short stature, obesity, subcutaneous nodules, short fourth metacarpals, and learning difficulties. There may be teeth enamel hypoplasia and calcification of the basal ganglia. ## **Treatment** - Treatment of acute symptomatic hypocalcaemia is with an intravenous infusion of calcium gluconate. - The 10% solution of calcium gluconate must be diluted as extravasation of the infusion will result in severe skin damage. - Chronic hypocalcaemia is treated with oral calcium and high doses of vitamin D analogues, adjusting the dose to maintain the plasma calcium concentration just below the normal range. - Hypercalcuria should be avoided as it may cause nephrocalcinosis, so urinary calcium excretion should be monitored.