Clinical presentation of hypopituitarism depends on the severity of the disease. It can be asymptomatic or mild to severe as in the case of a hypopituitary coma or an acute pituitary failure. In most patients the hypopituitarism presents itself as an endocrine dysfunction such as:

Adrenocorticotrophic deficiency

Acute symptoms include weakness, nausea, dizziness, vomiting, fever, circulatory collapse and shock. Chronic symptoms are fatigue, anorexia, weight loss and pallor. In children delayed puberty, failure to thrive, hypotension, anemia, hypoglycemia, lymphocytosis, eosinophilia and hyponatremia may occur.

Thyroid stimulating hormone deficiency

Various symptoms include weight gain, hypotension, bradycardia, cold intolerance, constipation, hair loss, cognitive slowing hoarseness and dry skin.

Growth hormone deficiency

Deficiency of growth hormone may result in a short stature, reduced muscle mass and strength, fatigue, visceral obesity, dyslipidemia, atherosclerosis, impaired memory and attention and a decreased quality of life. In children severe growth restriction has been documented.

Antidiuretic hormone deficiency

The symptoms of decreased antidiuretic hormone secretion include, a reduced urine osmolality, polydipsia, polyuria and hypernatremia.

• Fatigue

  In adults, the deficiency is linked to fatiguability, increased body fat, low muscle mass and a higher risk for the development of cardiovascular disease. [news-medical.net]

  Symptoms of ACTH and cortisol deficiency With gradual onset of deficiency over days or weeks, symptoms may include: Weight loss Fatigue Weakness Depression Apathy Nausea Vomiting Loss of appetite Abdominal pain As ACTH deficiency becomes more severe or [pacificneuroscienceinstitute.org]

  Symptoms and signs of central hypothyroidism might include weakness, fatigue, decreased energy, increased need for sleep, cold intolerance, and weight gain. [pituitaryworldnews.org]

  KEYWORDS: Fatigue; Hormones; Pituitary [ncbi.nlm.nih.gov]

• Weight Gain

  Symptoms and signs of central hypothyroidism might include weakness, fatigue, decreased energy, increased need for sleep, cold intolerance, and weight gain. [pituitaryworldnews.org]

  Clinical presentation is often insidious being characterized by non-specific manifestations, such as weight gain, fatigue, low muscle strength, bradipsychism, hypotension or intolerance to cold. [ncbi.nlm.nih.gov]

  Symptoms and Signs of Pituitary Hormone Deficiency Pituitary Hormone Target Organs Effect of Deficiency ACTH Adrenal glands: cortisol and DHEA Fatigue, low sodium in blood, weight loss, skin pallor TSH Thyroid gland: thyroid hormone Fatigue, weight gain [pituitarysociety.org]

  GH deficiency During childhood: dwarfism (see short stature ) During adulthood: usually asymptomatic; subtle findings include weight gain, weakness, and depression Prolactin deficiency Females: lactation failure following delivery Males: asymptomatic [amboss.com]

• Anemia

  Signs and symptoms of secondary hypothyroidism include fatigue, weakness, weight gain, thickened subcutaneous tissues, constipation, cold intolerance, altered mental status, impaired memory, and anemia. [emedicine.com]

  In addition, hair over the face, scrotum and body may be lost, along with bone and muscle loss, and anemia. [news-medical.net]

  In addition to severe growth retardation and pubertal delay, iron deficiency anemia and zinc deficiency were determined. His gliadin and endomysium antibodies were negative. [ncbi.nlm.nih.gov]

  Symptoms Fatigue Weight loss Decreased sex drive Decreased appetite Facial puffiness Anemia Infertility Women problems (hot flashes and periods) Decreased facial hair 10. [slideshare.net]

• Pallor

  Symptoms and Signs of Pituitary Hormone Deficiency Pituitary Hormone Target Organs Effect of Deficiency ACTH Adrenal glands: cortisol and DHEA Fatigue, low sodium in blood, weight loss, skin pallor TSH Thyroid gland: thyroid hormone Fatigue, weight gain [pituitarysociety.org]

  Observe eyelids, nails beds and skin pallor which indicate anemia. Ensure safety prequitions for patients with impaired visual field. Wet the eye with sterile water to provide comfort to the eye. [nursingexercise.com]

  A deficiency can lead to symptoms such as: Fatigue Low blood pressure Low serum sodium levels Low hemoglobin levels leading to pallor Low blood glucose In such patients, any crisis situation which puts increased stress on the body such as serious infections [news-medical.net]

  Chronic: fatigue, pallor, anorexia, weight loss. Acute: weakness, dizziness, nausea, vomiting, circulatory collapse, fever, shock. Children: delayed puberty, failure to thrive. [patient.info]

• Hypothermia

  May be triggered by infection, trauma, surgery, hypothermia or pituitary haemorrhage. [patient.info]

  A severe deficiency in TSH also has the potential to cause hypothermia, coma and death in rare cases. Children with abnormally low TSH levels are mentally and physically backward. [news-medical.net]

  TSH – central hypothyroidism, which can present in extreme state with myxedema coma à altered mental status, hypothermia, hypotension, bradycardia, hyponatremia, hypoglycemia, and CHF/cardiogenic shock ! 3. [errolozdalga.com]

  Some of the clinical features of hypopituitary coma include meningism, hormonal deficiencies, hypotension, ophthalmoplegia, reduced consciousness, visual field defects, hypoglycemia and hypothermia. [symptoma.com]

• Nausea

  Abstract A 50-year-old woman presented with a headache and nausea. A sellar and suprasellar mass was detected on MRI; the tumor was heterogeneously enhanced with gadolinium, and the pituitary stalk was slightly thickened. [ncbi.nlm.nih.gov]

  EMERGENCY Nausea, vomiting, extreme weakness, dehydration, and fever suggest adrenal insufficiency that may require emergency medical care. [healthcommunities.com]

  Symptoms of ACTH and cortisol deficiency With gradual onset of deficiency over days or weeks, symptoms may include: Weight loss Fatigue Weakness Depression Apathy Nausea Vomiting Loss of appetite Abdominal pain As ACTH deficiency becomes more severe or [pacificneuroscienceinstitute.org]

• Hypertension

  Univariate and multivariate logistic regression methods were used to analyze relationships between preoperative hypopituitarism and factors including age, sex, history of hypertension and secondary epilepsy, course of disease, tumor mass effect, site [ncbi.nlm.nih.gov]

  Prevalence of obesity was 44.8% (BMI) and 56.6% (waist circumference). 15.4% had diabetes (59.3% well controlled), 34.3% hypertension and 38.8% dyslipidemia. [endocrine-abstracts.org]

  Case 1 The patient was a newborn girl born after a full-term pregnancy, who was monitored due to increased biparietal diameter and lateral ventriculomegaly with colpocephaly, and no signs of intracranial hypertension. [elsevier.es]

  Patients with ischaemic heart disease were at increased risk and patients with hypertension, anaemia or proteinuria were at decreased risk of having multiple episodes of hypotension. [bmjopen.bmj.com]

• Orthostatic Hypotension

  The main types of hypotension are: Orthostatic hypotension: People with orthostatic hypotension (sometimes called postural hypotension) feel faint or lightheaded when they stand up or change position suddenly. [my.clevelandclinic.org]

  Hypotension is divided into several different classifications according to when your blood pressure drops. Orthostatic Orthostatic hypotension is the drop in blood pressure that occurs when you transition from sitting or lying down to standing. [healthline.com]

  Orthostatic Hypotension Orthostasis literally means standing upright. [ausmed.com]

  Low blood pressure due to nervous system damage (multiple system atrophy with orthostatic hypotension). [mayoclinic.org]

  Blood pressure - low; Postprandial hypotension; Orthostatic hypotension; Neurally mediated hypotension; NMH Calkins HG, Zipes DP. [medlineplus.gov]

• Arthralgia

  Within days, he developed severe fatigue, myalgias and arthralgias. Initial testing demonstrated central hypogonadism, followed by a low normal insulin-like growth factor-1 and an abnormal L-dopamine growth hormone stimulation test result. [ncbi.nlm.nih.gov]

  Signs and symptoms of ACTH deficiency may be profound and potentially fatal; they include myalgias, arthralgias, fatigue, headache, weight loss, anorexia, nausea, vomiting, abdominal pain, altered mentation or altered consciousness, dry wrinkled skin, [emedicine.com]

  Lean Tanned Tired Tearful Weakness Anorexia Dizzy Giants Flu-like myalgias/arthralgias Depression / psychosis / low self-esteem N&V, abdominal pain, diarrhoea / constipation No skin pigmentation as low ACTH – usually adrenal insufficiency e.g. with [almostadoctor.co.uk]

  Side effects may include soft tissue swelling and edema, arthralgias, myalgias, headache, and carpal tunnel syndrome. [endocrinologyadvisor.com]

• Euphoria

  Some individuals experience a pleasant “high” with supraphysiologic doses of glucocorticoid, leading them to complain when they are returned to true replacement doses.44 A patient’s desire for euphoria is not a reason to continue higher-than-replacement [medtextfree.wordpress.com]

• Vaginal Dryness

  dryness, absence of milk production in new mothers (Sheehan’s syndrome) In men: loss of libido and potency, reduced muscular strength, shrinking and softening of the testes, decreased secondary hair growth Hypopituitarism Diagnosis Patient history and [healthcommunities.com]

  Symptoms and Treatment of Gonadotropins deficiency: Women with hypogonadism develop: Menstrual irregularities Absence of periods (amenorrhea) Infertility Decreased libido Vaginal dryness Osteoporosis Our center individualizes care based on family history [pacificneuroscienceinstitute.org]

  Symptoms can include: In children, lack of growth In women, lack of menstrual periods and vaginal dryness In men, shrinking testicles and erectile dysfunction Confusion, weight gain, and constipation Weakness, low blood sugar, and feeling stressed Not [msdmanuals.com]

  In women, the symptoms may include: delayed menstrual periods reduction in libido vaginal dryness subfertility and infertility Affected women are also more likely to develop osteoporosis and weak bone structures prone to fractures later in life. [news-medical.net]

• Headache

  Abstract A 50-year-old woman presented with a headache and nausea. A sellar and suprasellar mass was detected on MRI; the tumor was heterogeneously enhanced with gadolinium, and the pituitary stalk was slightly thickened. [ncbi.nlm.nih.gov]

  Women who are postmenopausal will not have obvious symptoms such as these and may first present with headache or loss of vision. Men may also suffer sexual dysfunction as a result of gonadotropin deficiency. [medical-dictionary.thefreedictionary.com]

  It is associated with the sudden onset of headache accompanied or not by neurological symptoms involving the second, third, fourth and sixth cranial nerves. [dx.doi.org]

• Dizziness

  He complained of postural dizziness. A short synacthen test was performed which demonstrated a sub-optimal cortisol response, basal cortisol 217 nmol/l, 30 min post synacthen 463 nmol/l. [endocrine-abstracts.org]

  Symptoms of Hypopituitarism Growth retardation (children and adolescents) Partial or total sexual maturation impairment Weakness; dizziness or lightheadedness Nausea and vomiting; hoarseness Sensitivity to cold or difficulty staying warm Slow heartbeat [healthcommunities.com]

  Complications Even moderate forms of low blood pressure can cause dizziness, weakness, fainting and a risk of injury from falls. [mayoclinic.org]

  Even mild dehydration (a loss of as little as 1 percent to 2 percent of body weight) can cause weakness, dizziness and fatigue. [heart.org]

  (Sheehan’s syndrome- Sheehan’s syndrome is a condition that may occur in a woman who has a severe uterine haemorrhage during childbirth), Decreased serum level of prolactin, Papilledema, Low blood sugar, Hydrocephalus, Headache, Visual disturbance, Dizziness [nursingexercise.com]

Diagnosis of hypopituitarism is made based on various imaging and laboratory tests. Some of them are, MRI, CT Scan, levels of various hormones such as free thyroxin (FT4), thyroid-stimulating hormone (TSH), prolactin, luteinizing hormone (LH), testosterone and estradiol for men and women respectively in the blood.

Moreover the cortisol levels are assessed using provocative testing of the adrenal-pituitary axis. In some individuals the insulin tolerance tests may be required for a better assessment of the adrenocorticotropic hormone (ACTH), growth hormone (GH) and prolactin levels [9].

• Hypoglycemia

  The hypoglycemia was attributable to hyperinsulinism and was treated with diazoxide and chlorothiazide. She responded well, but the hypoglycemia returned after reducing the diazoxide. It was possible to stop the diazoxide after 2.5 years. [ncbi.nlm.nih.gov]

  The standard test for growth hormone deficiency is the insulin-induced hypoglycemia test. This test does carry some risk from the induced hypoglycemia. [medical-dictionary.thefreedictionary.com]

• Hyponatremia

  Often, hyponatremia is the only clue that a patient has hypopituitarism. [healio.com]

  BACKGROUND: Hyponatremia can unmask hypopituitarism and secondary adrenal insufficiency. This is important, since the need to screen for steroid deficiency, in patients with hyponatremia is often neglected. [ncbi.nlm.nih.gov]

  This differs from primary adrenal insufficiency, in which patients develop hyponatremia and hyperkalemia. Aldosterone secretion is not affected, as it does not depend on corticotropin but instead on the renin-angiotensin axis. [emedicine.com]

• Lymphocytosis

  Hypoglycaemia, hypotension, anaemia, lymphocytosis, eosinophilia, hyponatraemia. Thyroid-stimulating hormone (TSH) deficiency: See also the separate Hypothyroidism article. [patient.info]

  In children delayed puberty, failure to thrive, hypotension, anemia, hypoglycemia, lymphocytosis, eosinophilia and hyponatremia may occur. [symptoma.com]

Treatment of hypothyroidism is based on replacing the deficient hormones. Glucocorticoids must be administered in case of ACTH deficiency, in the case of an emergency such as a pituitary apoplexy or an obstetric pituitary hemorrhage. Gonadotropin deficiency is corrected by replacing the sex appropriate hormones, such as testosterone in men and estrogen replacement in women with or without progesterone replacement.

Growth hormone is not replaced often in adults unless symptom of GH deficiency arises [10]. Growth hormones are replaced in children whenever appropriate. Secondary hypothyroidism can be treated efficiently by thyroid replacement. In hospitalized patients on corticosteroids, the dose can be simply doubled up in case of a surgery.

Prognosis is mostly good, if the hormones are replaced sufficiently [7]. Though there is an increased morbidity among hypopituitarism patients, the reason for morbidity is not yet clearly understood [8].

Complications

The complications associated with hypopituitarism depend on the severity of the deficiency. Infection may be a major cause for complications. Some of the complications of hypopituitarism include amenorrhea, hypothyroidism, hypotension, infertility, osteoporosis, failure to develop during puberty and short stature.

Hypopituitarism can usually develop into hypopituitary coma due to pituitary apoplexy. Some of the clinical features of hypopituitary coma include meningism, hormonal deficiencies, hypotension, ophthalmoplegia, reduced consciousness, visual field defects, hypoglycemia and hypothermia.

Hypopituitarism can be caused by several factors as given below.

• Trauma of the head
• Brain surgery [1]
• Brain tumor [2]
• Radiation therapy [3]
• Stroke
• Inflammation or an infection of the brain tissues
• Tumor of the pituitary gland or the hypothalamus 
• Subarachnoid hemorrhage [4]

Apart from this hypopituitarism can also be caused by rare immune or metabolic diseases such as hemochromatosis, histiocytosis X, lymphocytic hypophysitis, sarcoidosis and a very rare condition following a pregnancy called the Sheehan`s syndrome.

Hypopituitarism is listed under the rare diseases by the National institute of health (NIH), as less than 200,000 people are affected by this in the United States. It has been estimated that 4.2 cases per 100,000 people are being reported every year, internationally [5].

According to a study conducted by Regal et al, it has been estimated that there is a prevalence of 45.5 cases for every 100,000 of the adult population [6].

The pituitary gland produces the trophic stimulus to the target glands. Hence when the trophic stimulus is impaired, the hormone production from the target gland is impaired resulting in the secondary failure of the target glands.

In normal cases, the secretion of the tropic stimulus is based on the subphysiological hormonal levels, by a feedback mechanism. But in case of hypopituitarism the levels of the trophic hormones are suboptimal or absent, resulting in reduced production of the target gland hormones.

Hypopituitarism can never be prevented, though it can be treated efficiently if detected early. Trauma to the pituitary gland can be minimized if hypophyseal surgery is carried out under high resolution microscopes. Obstetric pituitarism can be minimized by proper postpartum care. Minimum exposure of the pituitary gland during radiation therapy is mandatory to prevent hypopituitarism due to radiation exposure.

Hypopituitarism is a condition, where there is a decrease in hormones secreted by the pituitary gland. The pituitary gland is a small gland located below the brain. It secretes a number of important hormones such as the growth hormone, thyroid stimulating hormone, follicle stimulating hormone, luteinizing hormone, prolactin and adrenocorticotropic hormone.

These hormones play a major role in growth and development of the body and regulating the blood pressure and metabolism. Insufficient secretion of any of these hormones, can result in a dysfunction of that particular area, and is manifested by specific symptoms. Treatment includes the replacement of the deficient hormones by hormone replacement therapy.

Definition

Pituitary is a small pea-sized gland situated at the base of the brain. It is connected to the hypothalamus of the brain by a small stalk. The pituitary gland secretes a number of hormones such as the adrenocorticotropic hormone (ACTH), growth hormone (GH), prolactin, antidiuretic hormone and thyroid-stimulating hormone (TSH). 

Cause

Hypopituitarism occurs when there is a deficient secretion of one or many of these hormones. Some of the causes for hypopituitarism include, a tumor of the pituitary gland, radiation therapy involving the pituitary gland, trauma of the pituitary due to road accidents, autoimmune disorders affecting the pituitary, surgery involving the pituitary gland, severe infections such as meningitis that can affect the pituitary and many such. 

Symptoms

Hypopituitarism is marked by various symptoms like fatigue, undue tiredness, blackouts, loose stools, low blood pressure and such as a result of deficient ACTH. Deficiency of growth hormone may result in stunted growth, weakness and tiredness in adults. Low sex hormones can result in less sex drive in women and loss of libido in men, impotence, and irregular or absent menstrual periods. Less thyroid hormone can result in dry skin and tiredness. Lack of antidiuretic hormone can result in increased thirst and copious urine output.

Diagnosis

Hypopituitarism is usually diagnosed using blood tests to detect the hormone levels, visual field checks for ruling out tumors of the pituitary gland, MRIs and CT scans. 

Treatment

Treatment of hypopituitarism is done mainly by hormone replacement therapy.

1. Fernandez A, Brada M, Zabuliene L, Karavitaki N, Wass JA. Radiation-induced hypopituitarism. Endocr Relat Cancer. Sep 2009; 16(3):733-72
2. Fatemi N, Dusick JR, Mattozo C, et al. Pituitary hormonal loss and recovery after transsphenoidal adenoma removal. Neurosurgery. Oct 2008; 63(4):709-18; discussion 718-9.
3. Appelman-Dijkstra NM, Kokshoorn NE, Dekkers OM, et al. Pituitary dysfunction in adult patients after cranial radiotherapy: systematic review and meta-analysis. J Clin Endocrinol Metab. Aug 2011; 96(8):2330-40.
4. Gardner CJ, Javadpour M, Stoneley C, Purthuran M, Biswas S, Daousi C, MacFarlane IA, Cuthbertson DJ. Low prevalence of hypopituitarism after subarachnoid haemorrhage using confirmatory testing and with BMI-specific GH cut-off levels. Eur J Endocrinol. 2013; 168(4):473-81 (ISSN: 1479-683X)
5. Regal M, Paramo C, Sierra SM, Garcia-Mayor RV. Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol (Oxf). Dec 2001; 55(6):735-40.
6. Schneider HJ, Schneider M, Saller B, et al. Prevalence of anterior pituitary insufficiency 3 and 12 months after traumatic brain injury. Eur J Endocrinol. Feb 2006; 154(2):259-65.
7. Clayton RN. Mortality, cardiovascular events and risk factors in hypopituitarism. Growth Horm IGF Res. Feb 1998; 8 Suppl A: 69-76
8. Bulow B, Hagmar L, Eskilsson J, Erfurth EM. Hypopituitary females have a high incidence of cardiovascular morbidity and an increased prevalence of cardiovascular risk factors. J Clin Endocrinol Metab. Feb 2000; 85(2):574-84.
9. Asano T, Aoki A, Sasaki M, Ikoma A, Kakei M, Kawakami M, Ishikawa SE. Hyponatremia is the valuable manifestation for initiating diagnosis of hypopituitarism in elderly. Endocr J. 2012; 59(11):1015-20 (ISSN: 1348-4540)
10. Child CJ, Zimmermann AG, Woodmansee WW, et al. Assessment of primary cancers in GH-treated adult hypopituitary patients: an analysis from the Hypopituitary Control and Complications Study. Eur J Endocrinol. Aug 2011; 165(2):217-223.