Hypopituitarism

As for hypothalamic disease, because of the widespread functions of the pituitary gland (Dorton, 2000), there are many diseases associated with hypopituitarism. The term refers to an inability of the pituitary gland to provide sufficient hormones due to inadequate production or an insufficient supply of hypothalamic‐releasing hormones. When pituitary hormone production is impaired, target gland hormone production is reduced because of a lack of trophic stimulus. Normally, sub‐physiologic target hormone levels stimulate the pituitary gland to increase trophic hormone production; however, in hypopituitarism, the pituitary gland response is absent, suboptimal, or inappropriate. This results in progressive secondary failure of the target glands (Kim, 2015). It is usually a mixture of several hormonal deficiencies and can be chronic and lifelong, unless successful surgery or medical treatment of the underlying disorder can restore pituitary function (Schneider et al., 2007).

Children with hypopituitarism typically present with low target hormone levels accompanied by low or inappropriately normal levels of the corresponding trophic hormone (Coremblum, 2016). Thus, pituitary function is assessed by the target gland function, not by measuring the pituitary hormone as an isolated event. Symptoms depend on the degree and type of hormone depletion, the rapidity of onset and the specific condition that manifests as a result of reduced pituitary function.

Specific conditions caused by hypopituitarism are now described, namely: growth disorder, diabetes insipidus, and tumours of the pituitary gland.

Growth disorders

Growth disorders can be due to a number of constitutional and genetic causes such as achondroplasia, hypothyroidism, Cushing syndrome, Silver‐Russell syndrome, nutritional short stature, intrauterine growth restriction and bone disorders. The causation relevant to this chapter is short stature due to hormone deficiency in hypopituitarism. This type of growth disorder is characterised by growth that is very slow or delayed early in childhood before the ossification of bone cartilages (Dattani & Preece, 2004) and is caused by insufficient secretion of pituitary growth hormone.

The condition begins in childhood, and poor growth and/or shortness becomes more evident during puberty. It usually starts to show from late in the first year until mid‐teens. The most obvious sign is a noticeable slowing of growth. Children may also possess signs of low blood sugar or obesity but they display average body proportions and average intelligence (Human Growth Foundation, 2015).

Through the use of injections of synthetic human growth hormone (HGH) over a period of several years, these children can achieve average height.

Conversely, acromegaly is due to an over‐production of growth hormone during childhood characterised by excessive growth and height well above the average. Rarely, it affects children. If it develops in a child, usually between the ages of 15 and 17 years, it causes the condition known as gigantism and promotes growth of bones in the body.

Diabetes insipidus

Diabetes insipidus (DI) can be classified according to the primary cause. Neurogenic or cranial DI is of interest for this chapter, caused by a reduced amount of anti‐diuretic hormone (ADH) being produced and released by the pituitary gland. Other forms of DI are nephrogenic DI, which originates in the kidney where the renal tubules are unresponsive to ADH, and idiopathic DI where the cells in the hypothalamus become damaged by an autoimmune response and stop producing ADH.

ADH, also called arginine vasopressin, is a hormone that constantly regulates and balances the amount of water in the blood. Osmoreceptors in the hypothalamus cells detect changes in the osmotic pressure in blood capillaries. A nerve message is sent to the pituitary to release ADH, which then travels in the blood to the kidneys. ADH increases the permeability of the distal tubule and collecting duct, so more water is reabsorbed. This causes the urine to be more concentrated. Osmoreceptors also regulate the body’s sense of thirst. However, if less ADH is released, an increased volume of dilute urine will be passed (Roth & Kemp, 2015) and the child will become more thirsty leading to neurogenic DI. Signs and symptoms therefore include excessive thirst and excessive urination (Khardori & Ulla, 2012). Signs of dehydration may ensue if this condition continues without recognition or diagnosis. Neurogenic DI may just be a problem on its own but it can also occur with other problems because the production of other hormones that are released by the pituitary gland is also affected. For an example of the presenting signs of diabetes insipidus, refer to Case Study 1 at the end of this chapter.

For neurogenic DI, the treatment of choice is the synthetic ADH analogue desmopressin (1‐deamino‐8‐D‐arginine vasopressin [DDAVP]) (Mishra & Chandrashekhar, 2011). Parents must be educated regarding water replacement in infants and young children who cannot express thirst or access fluids without assistance. Gastrointestinal illnesses that cause decreased intake, increased stool losses, or both, must receive early and serious attention to prevent life‐threatening electrolyte and fluid balance abnormalities (Roth & Kemp, 2015).

Tumours of the pituitary gland

Tumours can also be a cause of pituitary dysfunction. They are usually benign and can cause problems either due to local effects of the tumour, or because of excessive hormone production or inadequate hormone production by the remaining, unaffected pituitary gland. Pituitary tumours include:

• Craniopharyngioma: a benign tumour that develops near the pituitary gland. This tumour most commonly affects children 5–10 years of age.
  
• Pituitary adenoma: a small, benign tumour, usually less than 1 cm in size, which is made of abnormal cells that produce ACTH. This stimulates the adrenal glands, which then release cortisol. The abnormal cells in the adenoma are not downregulated by feedback from the high levels of cortisol. Excluding cases caused by steroid medication, the majority of cases of Cushing syndrome in children are caused by a pituitary adenoma.
  
• Prolactinoma: a non‐cancerous swelling that produces excess prolactin.
  
• Others: Growth hormone (GH)‐secreting, thyroid‐stimulating hormone‐secreting, and luteinising hormone/follicle‐stimulating hormone (LH/FSH)‐secreting tumours, named according to the hormone that is produced in excess (Keil & Stratakis, 2008).

Tumours can potentially cause symptoms in the following ways:

• by increasing intracranial pressure on the brain;
  
• by disrupting the function of the pituitary gland and the related hormones;
  
• by damaging the optic nerve.

In craniopharyngioma, increased pressure on the brain causes headache, nausea, vomiting and difficulty with balance. Damage to the pituitary gland causes hormone imbalances that can lead to various problems with the associated functions of those hormones, such as DI and stunted growth. When the optic nerve is damaged by the tumour, visual problems can develop. These defects are often permanent and may get worse after surgery to remove the tumour. Children will show evidence of decreased hormone production at the time of diagnosis. Investigations for diagnosis include:

• endocrine hormone evaluations to look for any imbalances (see Investigations box: Assessing endocrine function);
  
• CT scan or MRI scan of the brain;
  
• neurological examination.

In pituitary adenoma, the onset of the signs of Cushing disease may be insidious. Growth failure or deceleration associated with weight gain is a hallmark of Cushing syndrome in children. Other signs and symptoms often seen in children and adolescents with this condition include facial plethora, increased fine downy hair on the face, body and extremities, a temporal fat pad, round face, and diabetes. In prolactinoma, this can cause various symptoms including reduced fertility, breast changes, and headaches. In children there may be reduced growth or delayed puberty.

The management of the condition depends on the tumour. Traditionally, surgery has been the main treatment for craniopharyngioma but radiation treatment instead of surgery may be the best choice for some patients. In tumours that cannot be removed completely with surgery, radiation therapy is usually necessary. A biopsy may not be necessary if treatment with radiation alone is planned. In general, the prognosis for patients with craniopharyngioma is good, with an 80–90% chance of permanent cure if the tumour can be completely removed with surgery or treated with high doses of radiation. Recurrences may occur within the first 2 years after surgery. The prognosis for an individual child depends on whether the tumour is completely removed and the neurological deficits and hormonal imbalances caused by the tumour and the treatment. A significant percentage of patients have long‐term hormonal, visual, and neurological problems following the treatment of craniopharyngioma. In patients where the tumour is not completely removed, the condition may recur (Maity et al., 2008).

For a pituitary adenoma, the first‐line treatment in childhood is surgical in the form of an adenomectomy or radiation for children in whom surgical intervention has failed (Keil & Stratakis, 2008). Prolactinomas can be treated successfully usually with medication using dopamine agonists to shrink the mass (Colao & Loche, 2009).