Panhypopituitarism is a disorder that results from the underactivity or the inability of the anterior pituitary gland to secrete essential hormones for the body. This is usually a complication of disorders that affect the pituitary glands either by reducing or destroying its function or interfering the secretion of pituitary releasing hormones by hypothalamus.
Children with congenital midline defects or optic atrophy (which suggests the presence of septo-optic dysplasia)   and boys with micropenis due to deficit gonadotropin hormones (GH)   should be suspected to have hypopituitarism. However, there are children without any findings of hypothalamus or pituitary-related conditions, but are still diagnosed with hypopituitarism. In cases like these, the child only shows stunted growth due to deficient GH.
Central hypopituitarism is found in some children who require medical attention due to abnormal thyroid functions. Girls with this condition may experience amenorrhea, either primary or secondary. Growth failure is the most commonly seen feature of hypopituitarism. It is seen as a decrease in growth rate for age. The clinical presentation of the condition is dominated by the underlying pathology, its speed of onset and severity of hypopituitarism. Space-occupying lesions that cause hypopituitarism may lead to symptoms such as visual abnormalities, headache and rarely, changes in personality, cerebrospinal fluid (CSF) rhinorrhea and temporal lobe epilepsy.
Less severe ACTH deficiency can manifest along with other illnesses, however, pituitary apoplexy can result in severe hypopituitarism which presents as a medical emergency.
Panhypopituitarism may present in the child acutely with deficient cortisol or thyroid hormones or chronically with a continuous and progressive deficiency in pituitary hormones. Nonspecific symptoms are most frequently seen in the form of exercise intolerance, abdominal pain, loss of axillary and pubic hair weakness or fatigue, Increase in weight, decrease in libido, and irregular menstruation.
Hormones affected in hypopituitarism have different physiological effects in children. A deficiency in gonadotropic hormone can affect the metabolism and growth, causing hypoglycemia and stunted height. Gonadotropin deficiency results in prenatal micropenis and in older children cause interrupted or delayed puberty. Deficiency of corticotrophin hormone interferes the metabolism of carbohydrate, protein, and lipid molecules resulting in weight loss, hypotension, hypoglycemia, weakness and in worst cases, death of patients. Hypothyroidism results from thyrotropin hormone deficiency results. Its diagnosis is often missed as the clinical manifestations may be non-specific and depends upon the extent of hormone deficiency. Besides various signs and symptoms resulting from the pressure effects on the pituitary gland and stalk, a complex picture of hormone excess and deficiency can be produced by actively secreting tumors e.g. macroadenoma secreting GH causing hypogonadism and acromegaly.
Pituitary hormone loss is a progressive and slow process which may take several months or years. Occasionally hypopituitarism starts suddenly rapid development of symptoms. It is the growth hormone which is affected first in hypopituitarism, followed by luteinizing hormone. Adrenocorticotropin (ACTH), follicle-stimulating hormone (FH), prolactin and thyroid stimulating hormone (TSH) are lost much later in the stage .
Diagnosing a child with hypopituitarism can be done by determining the hormonal deficiency and identifying the cause. It consists of a detailed clinical examination and biochemical studies.
Hypothyroidism, which occurs secondary to the TSH deficiency is easiest to diagnose. Head MRI should be done in all the children suspected to have with panhypopituitarism. This is an important step to determine underlying tumors or structural abnormalities potentially causing the condition .
Also, due to frequent delay in bone age in patients with hypopituitarism, a left hand and wrist radiography are helpful in determining bone age. Though, it has found to have low sensitivity and specificity. Visual field examination is important while doing the physical examination. Simultaneous assessment of basal anterior pituitary and target organ hormone helps in providing important information to establish the cause of hypopituitarism. Baseline tests include thyroxine, TAH, FSH, LH, prolactin, testosterone/estradiol, 9 am cortisol and insulin-like growth factor 1.
Evidence of hypopituitarism from clinical and biochemical studies would then necessitate imaging studies of the hypothalamic‐pituitary region. MRI is the investigation of choice . A CT scan with contrast is a good alternative in cases where MRI study is not possible.
The treatment of panhypopituitarism is directed towards the underlying cause and the replacement of deficit hormones. Management involves surgery, medical therapy, radiotherapy or a combination of any of these options. Cases of GH secreting microadenoma are managed best with surgical excision of the tumor  whereas, treatment with dopamine agonists is required in cases of macroprolactinoma . In cases where pituitary or peripituitary tumors do not respond to medical management and causes pressure effects, surgery is the usually required option.
Assessment of the pituitary hormone status is necessary after treatment to determine the functional improvement  . Target hormone replacement is done in all cases except those with ADH or GH deficiency or in cases of desired fertility, where deficit hormone is replaced. All the deficit hormones are replaced in panhypopituitarism and lifelong hormone replacement is required. The goal of hormone replacement is to achieve the desired levels of circulating hormones in the blood, to maintain the normal physiology and avoid deficiency symptoms with least side effects.
Thyroid hormone deficiency is replaced by L-thyroxine, which is given empty stomach at 100-150 ug every morning. The aim of the therapy is to attain the normal T4 levels. deficiency of adrenal hormones is managed by hydrocortisone or prednisone, which stimulate the normal circadian rhythm of cortisol. In women with ACTH deficiency low doses of dehydroepiandrosterone are useful. Deficiency of FSH or LH depends on the gender and desire for fertility. Estrogen and progesterone are required in premenopausal women. Testosterone is only required in men with hypogonadism without desiring fertility. In severe growth hormone deficiency, GH therapy is beneficial. It is given as a subcutaneous injection once daily, usually in the evening time. GH therapy helps with exercise capacity, skeletal integrity, body composition and improves quality of life.
Adrenal crisis is the most common acute complication that can result from the medical management of hypopituitarism. Adrenal crisis occurs when glucocorticoid hormone therapy is administered inappropriately or when a child has a concurrent illness that requires increasing doses of glucocorticoids. Meticulous monitoring is the best approach to prevent any adverse effects from thyroid supplements or sex steroid therapy. Stable patients usually have a favorable outcome with hormonal therapy.
Acquired panhypopituitarism is commonly associated with hypothalamic or pituitary tumors and surgical or radiological treatment associated with them. Craniopharyngiomas, optic gliomas and pituitary dysgerminomas have been identified as one of the common causes panhypopituitarism . Deficiencies of pituitary hormones are seen in various congenital midline defects such as septo-optical dysplasia (also known as the de Morsier syndrome), facial clefts, or the presence of a single central incisor . About three fourths of patients diagnosed with optic nerve hypoplasia were found to have abnormal hormone levels in blood . The common causes of panhypopituitarism in adults are pituitary gland adenomas, post radiation therapy, sellar mass lesions, Sheehans syndrome, pituitary gland apoplexy, granulomatous infiltrative conditions and empty sella syndrome. The characteristic imaging finding is seen in most of these etiologies.
Panhypopituitarism that results from genetic mutation can have normal neuroimaging results, but the defects appear early in the life and not in the adulthood . Of all the different causative conditions for adult hypopituitarism, pituitary adenoma and its treatment either by surgery or radiation therapy is found to be most frequently seen.
Regal, et al  released a report showing the prevalence of panhypopituitarism as 45 in every 100,000 individuals. The incidence rate was found to be 4 per 100,000 per year in normal population. Approximately 50% of subjects found to have deficiency of three to five pituitary hormones.
Reduction of pituitary hormones results in impairment of target hormone production due to the loss of trophic stimuli. Normally, target hormones at their sub physiologic levels stimulate the pituitary gland, resulting in the increased production of trophic hormones. In hypopituitarism, due to the decreased or absent response of the pituitary gland, production of target hormones is decreased. Hence, the patient presents with low levels of trophic hormones in the presence of low target hormone levels.
Macroadenomas greater than 1 cm in diameter can be linked to one or more trophic hormonal deficiencies in 30% of patients  as a result of direct compression. Consequentially, the destruction of the proximal normal tissue from prolonged compression leads to glandular hyposecretion. Other possible mechanisms for the development of panhypopituitarism includes a primary effect of a tumor mass on the vascular portal system (also called the pituitary stalk), elevated intrasellar pressure that later affects portal circulation, and focal necrosis of pituitary tissues that resulted from prolonged inefficient supply of portal blood  . Functions of the pituitary gland are rarely affected by microadenomas that are less than 1 cm . Microadenomas that secrete prolactin often manifest with symptoms of hypogonadism due to the suppression of gonadotrophins production (follicle-stimulating hormone FSH and luteinising hormone LH) by prolactin.
Children who are diagnosed with hypopituitarism may require close monitoring and continuous assessment by a pediatric endocrine specialist. Regular monitoring of physical growth and free T4 levels is required to measure the efficiency of T4 replacement. Signs and symptoms of cortisol excess or deficiency are helpful in determining the efficiency of cortisol replacement therapy. Monitoring of pubertal status is important. It also helps in determining any risks involved with sex or thyroid hormone treatment.
Panhypopituitarism is characterized by an inadequacy or deficiency of hormone produced by the anterior part of the pituitary gland. It commonly occurs due to other secondary causes that affect the pituitary gland, either by interfering with the hypothalamic secretion of pituitary hormones or by destroying or reducing it function. A deficiency of one or more pituitary hormones occurs in underactive pituitary gland. Panhypopituitarism can occur due to several factors, including pituitary gland tumors, certain inflammatory conditions or decreased blood supply to the gland.
The diagnosis is made by assessing the levels of pituitary hormones in the blood and imaging studies of the gland. Treatment involves surgical removal of pituitary tumors, replacement of the deficient hormone with the synthetic one or radiation therapy.