Signs such as increased body fat and waist-hip ratio, reduction in lean body mass, low muscle strength and endurance are some of the findings seen in GHD patients [11]. An evidently short stature for appropriate age or reduced height velocity over the course of few years and neurological deficits that may point to intracranial lesions (anosmia or visual deficits) are findings that require exclusion of GHD as the underlying cause, while neonatal signs include prolonged jaundice, microcephaly and hypoglycemia [3].

• Short Stature

  Short stature is one of the clinical manifestations in these children. Although polyuria, polydipsia, hypokalemia, and salt loss may be responsible for growth retardation, the exact pathogenesis of short stature in Bartter syndrome is not known. [ncbi.nlm.nih.gov]

  ACMG practice guideline: genetic evaluation of short stature. Genet Med. 2009 Jun;11(6):465-70. doi: 10.1097/GIM.0b013e3181a7e8f8. Erratum in: Genet Med. 2009 Oct;11(10):765. Wit JM, Kiess W, Mullis P. Genetic evaluation of short stature. [ghr.nlm.nih.gov]

  Severe constitutional short stature amenable to GH therapy. • Turner Syndrome (Confirmed by chromosome analysis) • 3. [slideshare.net]

• Pain

  Joint pains. 3. Muscle pains. 4. Tingling, numbness, usually at the wrist. 5. Carpal tunnel syndrome. 6. Headache. These side-effects are usually due to a large initiating dose of growth hormone and usually subsides by reducing the dose. [onlinemedinfo.com]

  The second one aged 34 with impaired fasting glycemia and without any sign of GHD presented with sudden calf pain as a result of tibial posterior arterial acute occlusion. [ncbi.nlm.nih.gov]

  If the person is getting too much growth hormone, he or she will have muscle or joint pain, swelling (fluid retention) and pain or numbness in the hands from carpal tunnel syndrome. [cedars-sinai.edu]

  The most common side effects reported are: An injection site reaction such as pain, numbness, redness, and swelling Muscle and joint pain Tingling and numbness Unusual skin sensations Headache Adults also commonly report swelling associated with fluid [saizenus.com]

  The symptoms might include swelling in the hands and feet, pain in the large joints, and carpal tunnel syndrome. [ccpd.ucsf.edu]

• Fatigue

  CASE PRESENTATION: Here, we describe a 17-year old boy referred to our hospital for fatigue, decreased muscle strength and severe headache reported after the cessation of rhGH treatment for a GH deficiency diagnosed at the age of 2 years and 3 months. [ncbi.nlm.nih.gov]

  Three cytokines, IL-1, IL-6, and IL-8, cause severe widespread pain, fatigue and disturbed sleep. IL-6 is related to fatigue and impaired concentration. [worldhealth.net]

  Of these, the most frequently cited were sleep troubles, and fatigue. Respondents had difficulty falling asleep or sleeping through the night, and were deeply fatigued during the day. [bmcresnotes.biomedcentral.com]

  Clinical Features of Growth hormone deficiency Fatigue. Muscle weakness. Reduced exercise capacity. Weight gain. Increase in body fat and decrease in muscle mass. [onlinemedinfo.com]

  Adults with growth hormone deficiency often have poor bone density and reduced muscle mass, and mental and emotional symptoms, such as fatigue, depression, and poor memory, are also common. [endocrineweb.com]

• Weight Gain

  We diagnosed GHD at age 8 yr 8 months because of growth deceleration (from 95 to 25%) and abnormal growth rate (3 cm/yr) despite euthyroidism, fair glycemic control, and normal weight gain. [ncbi.nlm.nih.gov]

  Our goal is to improve our patients' overall sense of well-being and reverse symptoms, such as weight gain and poor bone density. [ucsfhealth.org]

  The goal of therapy for adults is to improve the overall sense of well-being and reverse the symptoms and signs of growth hormone deficiency, such as weight gain and poor bone density. [ccpd.ucsf.edu]

  Weight gain. Increase in body fat and decrease in muscle mass. Increase in LDL cholesterol (bad cholesterol) and triglycerides and decrease in HDL cholesterol (good cholesterol). Increased risk for heart attack, heart failure and stroke. [onlinemedinfo.com]

• Swelling

  The symptoms might include swelling in the hands and feet, pain in the large joints, and carpal tunnel syndrome. [ccpd.ucsf.edu]

  Edema (swelling). 2. Joint pains. 3. Muscle pains. 4. Tingling, numbness, usually at the wrist. 5. Carpal tunnel syndrome. 6. Headache. [onlinemedinfo.com]

  If the person is getting too much growth hormone, he or she will have muscle or joint pain, swelling (fluid retention) and pain or numbness in the hands from carpal tunnel syndrome. [cedars-sinai.edu]

  Hand swelling and stiffness, joint and muscle ache, and insulin resistance are the most common side effects. In addition, there are reports linking increased cancer risks with increased GH activity/IGF-1 levels in population studies. [healthcentral.com]

• Anosmia

  An evidently short stature for appropriate age or reduced height velocity over the course of few years and neurological deficits that may point to intracranial lesions (anosmia or visual deficits) are findings that require exclusion of GHD as the underlying [symptoma.com]

  Panel 2: Some developmental defects associated with GHD Optic nerve hypoplasia - a developmental defect of the optic nerve which leads to defective vision Anosmia - loss of smell Anencephaly - a large defect in the skull with a rudimentary brain Holoprosencephaly [pharmaceutical-journal.com]

• Jaundice

  The proband is a 5-year-old girl who presented with neonatal hypoglycaemia and prolonged jaundice. No definitive endocrine cause of hypoglycaemia was identified in the neonatal period. [ncbi.nlm.nih.gov]

  Newborns with growth hormone deficiency may have low blood sugar (hypoglycemia), jaundice (hyperbilirubinemia), or other congenital abnormalities such as a small penis (micropenis) in males or face defects (such as a cleft palate). [msdmanuals.com]

  About 10 percent of infants with alpha-1 antitrypsin deficiency develop liver disease, which often causes yellowing of the skin and whites of the eyes (jaundice). [ghr.nlm.nih.gov]

  • Increased fat • Short stature • High pitched voice • Perinatal hx: pregnancy, perinatal events, prolonged jaundice • Micropenis, undescended testis. • Increased fat • High pitched voice • Low threshold for hypoglycemia 17. [slideshare.net]

• Osteoporosis

  She was for the first time diagnosed as panhypopituitarism including growth hormone deficiency and osteoporosis by endocrine examinations and bone mineral densitometry, respectively. [ncbi.nlm.nih.gov]

  • ↓Exercise capacity, ↓max O2 intake • ↓ bone mass (osteopenia/osteoporosis), ↓body hair. 22. [slideshare.net]

  In adults, symptoms include: Decreased energy Increase in fat and decrease in lean muscle mass Difficulty exercising Osteoporosis Sleep disturbance Skin changes (fine lines, dryness, thinning) Psychological symptoms, such as depression and feelings of [ucsfhealth.org]

  In adults symptoms include: decreased energy a feeling of social isolation increase in fat and decrease in lean muscle mass poor exercise tolerance osteoporosis sleep disturbance skin abnormalities (fine wrinkling, dryness, thinning) Some studies show [ccpd.ucsf.edu]

• Decreased Muscle Mass

  Anxiety and/or depression Baldness (in men) Decrease in sexual function and interest Decreased muscle mass and strength Difficult to concentration and lack of memory Dry, thin skin Elevated triglyceride levels Fatigue and/or tiredness Heart problems High [endocrineweb.com]

  In adults, growth hormone deficiency has multiple effects, including: Altered body composition with increased fat mass and decreased muscle mass Decreased exercise capacity Increase in LDL cholesterol (bad cholesterol) Low bone mineral density Decreased [endo.wustl.edu]

  […] strength and exercise tolerance Decreased muscle mass Weight gain, especially around the waist Feelings of anxiety, depression, or sadness causing a change in social behavior Thin and dry skin When Should I Seek Medical Care for Growth Hormone Deficiency [emedicinehealth.com]

• Arthralgia

  A total of 55.2% of patients were reported to have experienced adverse events (AEs), including arthralgia, myalgia, abdominal distension and hypoaesthesia, and 4.5% had adverse drug reactions. [ncbi.nlm.nih.gov]

  GH REPLACEMENT THERAPY: SE Common: Edema, arthralgias, and myalgias Others: Atrial fibrillation Iatrogenic acromegaly Benign intracranial hypertension Increase in melanocytic nevi Carpal tunnel syndrome Muscle stiffness Headache Paresthesias Hyperglycemia [slideshare.net]

  Of the remaining 5 patients in the GH group, 2 patients withdrew from the study because of arthralgia, 2 patients for personal reasons, and 1 patient underwent cardiac transplantation. [heartfailure.onlinejacc.org]

  Table 3: Common adverse reaction rates Adverse reaction Occurrence (per cent) Fluid retention 37.4 Arthralgia 19.1 Muscle pains 15.7 Contraindications Absolute contraindications include evidence of any active tumour, BIH, pregnancy, and post-renal transplantation [pharmaceutical-journal.com]

  […] appropriate dosage may be monitored through regular evaluation of serum IGF-1, and IGF-1 should be in the upper half of the physiological range throughout therapy. rhGH is rather safe to use, as side effects are very rarely encountered, most common being arthralgia [symptoma.com]

• Severe Short Stature

  We report on a genetically diagnosed NS/LAH patient manifesting severe short stature (-3.85 SDs) with low serum level of IGF1, 30 ng/ml. [ncbi.nlm.nih.gov]

  By definition, about 2.5% of children show a short stature due to several causes. [hindawi.com]

• Myalgia

  A total of 55.2% of patients were reported to have experienced adverse events (AEs), including arthralgia, myalgia, abdominal distension and hypoaesthesia, and 4.5% had adverse drug reactions. [ncbi.nlm.nih.gov]

  GH REPLACEMENT THERAPY: SE Common: Edema, arthralgias, and myalgias Others: Atrial fibrillation Iatrogenic acromegaly Benign intracranial hypertension Increase in melanocytic nevi Carpal tunnel syndrome Muscle stiffness Headache Paresthesias Hyperglycemia [slideshare.net]

  Overall, rhGH is believed to be safe and significant side-effects in children are very rare, including benign intracranial hypertension, hyperglycaemia, arthralgia and myalgia. [intechopen.com]

  Side effects Most of the reported side effects are the result of GH-induced fluid retention and include edema, arthralgia, myalgia, paresthesia and carpal tunnel syndrome. [louvainmedical.be]

  Initiating therapy at low doses (total dose 0.2–0.4 mg/day SC) decreases the likelihood of developing common side effects like joint stiffness, arthralgias, myalgias, paresthesias, and peripheral edema, with fluid retention. [frontiersin.org]

• Alopecia

  The non-inflammatory type usually will not be complicated by scarring alopecia. [ncbi.nlm.nih.gov]

  Tinea capitis causes the gradual appearance of round patches of dry scale, alopecia, or both. [merckmanuals.com]

  Scaling of the scalp and a black-dot alopecia were also observed. Apart from the skin lesions, the general condition of the patient was good. The results of blood and urine tests were normal. [medicaljournals.se]

  […] termed kerion, with the potential for scarring and permanent alopecia. [emedicine.medscape.com]

  Favus form is caused by Trichophyton schoenleinii and is characterized by yellow crust around the hair shafts and can result in permanent scarring alopecia [1]. [karger.com]

• Dry Skin

  Adults who develop growth hormone deficiency may report central weight gain, difficulty to lose weight, dry skin, fatigue, and often do not feel their usual selves. Most notice a decrease in their physical energy level and endurance for exercise. [magicfoundation.org]

• Thin Skin

  Anxiety and/or depression Baldness (in men) Decrease in sexual function and interest Decreased muscle mass and strength Difficult to concentration and lack of memory Dry, thin skin Elevated triglyceride levels Fatigue and/or tiredness Heart problems High [endocrineweb.com]

  Symptoms of GHD in adults include: Increased fat, especially around the waist Lower muscle mass and strength Mild bone loss Thinning skin Sleep problems Decreased exercise performance Decreased energy Decreased well-being, mild depression, or moodiness [hormone.org]

• Mood Swings

  Respondents struggled with body and self-image and reported a wide range of emotional impacts of AGHD, including frustration, anxiety, anger or resentment, depression, irritability, and mood swings. [bmcresnotes.biomedcentral.com]

  […] hormone deficiency and other endocrine disorders. * Fatigue * Increased Fat around the Waistline * Loss of muscle mass or decreased strength * Insomnia * Decreased mental concentration * Poor Memory * Decreased Sexual Function or Drive * Depression or Mood [drmarinajohnson.com]

• Headache

  CASE PRESENTATION: Here, we describe a 17-year old boy referred to our hospital for fatigue, decreased muscle strength and severe headache reported after the cessation of rhGH treatment for a GH deficiency diagnosed at the age of 2 years and 3 months. [ncbi.nlm.nih.gov]

  They include: Headaches Muscle or joint pain Mildly under active thyroid gland Swelling of hands and feet Curvature of the spine (scoliosis) Development of breast tissue in boys Rare but serious side effects include: Severe headache with vision problems [hormone.org]

  • Headaches • Visual disturbances • Symptoms of chronic illness • Family history of delayed growth • Symptoms of other associated hormonal deficiencies. 18. [slideshare.net]

  Symptoms Slow growth or absence of growth Short stature (below the fifth percentile compared to other children of the same age and sex) Absent or delayed sexual development during puberty Headaches Symptoms of other pituitary hormone deficiencies that [hopkinsmedicine.org]

• Sleep Disturbance

  In adults symptoms include: decreased energy a feeling of social isolation increase in fat and decrease in lean muscle mass poor exercise tolerance osteoporosis sleep disturbance skin abnormalities (fine wrinkling, dryness, thinning) Some studies show [ccpd.ucsf.edu]

  In adults, symptoms include: Decreased energy Increase in fat and decrease in lean muscle mass Difficulty exercising Osteoporosis Sleep disturbance Skin changes (fine lines, dryness, thinning) Psychological symptoms, such as depression and feelings of [ucsfhealth.org]

  Three cytokines, IL-1, IL-6, and IL-8, cause severe widespread pain, fatigue and disturbed sleep. IL-6 is related to fatigue and impaired concentration. [worldhealth.net]

• Memory Impairment

  Finally, patients with GH deficiency appear to have impaired psychological well being and potentially significant neuropsychiatric manifestations, such as lack of concentration and memory impairment. [pituitary.mgh.harvard.edu]

  Patients with GHD appear to have impaired psychological well-being and potentially significant neuropsychiatric manifestations, such as difficulty concentrating and memory impairment (McGauley et al., 1990). [frontiersin.org]

  Patients with GHD appear to have impaired psychological well-being and potentially significant neuropsychiatric manifestations, such as difficulty concentrating and memory impairment ( McGauley et al., 1990 ). [journal.frontiersin.org]

A detailed physical examination and patient history are key initial steps in the diagnostic workup, in order to assess the present signs and symptoms that may point to GHD. Basic laboratory findings may reveal a reduced GFR, dyslipidemia and impaired glucose levels [1] [11]. Endocranial MRI is a pivotal imaging procedure, as it may point to a lesion responsible for suppressed GH production, such as a tumor or other infiltrative diseases [3]. Evaluation for other pituitary hormone deficiencies (TSH, FH, LH, ACTH) should be performed as well, since individuals that have 3 or more pituitary hormone deficiencies can be almost definitely diagnosed with GHD without the use of GH stimulation test, an invasive and time-consuming, but also dangerous procedure because of potentially severe side effects [5]. Although GH stimulation (also known as insulin tolerance test, or ITT ) is considered to be the gold standard for the diagnosis, it is contraindicated in patients who report a history of seizures or ischemic heart disease [1] [3]. Additionally, false-positive values may be obtained in morbidly obese patients. For this reason,an introduction of alternative diagnostic methods, such as GH-releasing peptide-2 (GHRP-2) test into regular practice is becoming more common, since they are safe and more convenient [1]. Measurement of IGF-1 has also been recommended in GHD patients and values below normal are highly indicative of the diagnosis, but some patients may present with IGF-1 levels within physiological limits, in which case other tests need to be used for confirmation [1].

• Hypoglycemia

  Hypoglycemia is potentially life-threatening, especially in infants, and can be due to congenital cortisol and/or GH deficiency (GHD). [ncbi.nlm.nih.gov]

• Cholesterol Increased

  Increase in body fat and decrease in muscle mass. Increase in LDL cholesterol (bad cholesterol) and triglycerides and decrease in HDL cholesterol (good cholesterol). Increased risk for heart attack, heart failure and stroke. [onlinemedinfo.com]

  Decreased glycogen stores Increased insulin resistance in first six weeks with return to baseline by three months Lipid metabolism Increased total and LDL-cholesterol Increased triglyceride Decreased HDL-cholesterol Decrease or no change in total and [pharmaceutical-journal.com]

  particularly raised LDL cholesterol Increased levels of fibrinogen and plasminogen activator inhibitor Cardiac dysfunction, including a thickened intima media Lack of well-being Depression and anxiety Social isolation Fibromyalgia syndrome Neuromuscular [en.wikipedia.org]

• Dyslipidemia

  Basic laboratory findings may reveal a reduced GFR, dyslipidemia and impaired glucose levels. [symptoma.com]

  Dyslipidemia and hyperuricemia were the most common metabolic disturbances in Chinese patients. [ncbi.nlm.nih.gov]

  […] children with growth hormone (GH) deficiency is due almost entirely to other pituitary hormone deficiencies. [1] These children have an increased relative risk of death in adulthood from cardiovascular causes resulting from altered body composition and dyslipidemia [emedicine.medscape.com]

  The fat accumulation is preferentially intra-abdominal, a distribution that has been associated with dyslipidemia, insulin intolerance, hypertension and some malignancies (breast and colon). [myalgia.com]

• LDL Cholesterol Increased

  Metabolism Lipid metabolism Most studies in AOGHD subjects demonstrate an increase in total cholesterol, LDL-cholesterol and triglyceride levels, in association with a low HDL level. [pharmaceutical-journal.com]

  particularly raised LDL cholesterol Increased levels of fibrinogen and plasminogen activator inhibitor Cardiac dysfunction, including a thickened intima media Lack of well-being Depression and anxiety Social isolation Fibromyalgia syndrome Neuromuscular [en.wikipedia.org]

Substitution with GH is the cornerstone of treatment in all patients, but the optimal dose depends on age, gender, percentage of adipose tissue and additional drug use, which may present a challenge for the physician [1]. Recombinant human GH (rhGH) has become available in recent years and is recommended in a treatment of various diseases that disrupt the pituitary gland and GH concentrations [6]. It must be stated that the dose should never be titrated according to body weight and all of the mentioned factors should be taken into consideration [1]. In general, a dose of approximately 0.1 mg/day in the evening should be given when initiating treatment through subcutaneous injections and a gradual increase in dosing is recommended based on the individual response and laboratory values [1]. In women who receive estrogen, a higher GH dose is required, especially if estrogen is taken orally, as it interferes with GH and hepatic IGF-1 [1]. The appropriate dosage may be monitored through regular evaluation of serum IGF-1, and IGF-1 should be in the upper half of the physiological range throughout therapy [1]. rhGH is rather safe to use, as side effects are very rarely encountered [1] [12], most common being arthralgia and edema as a result of water retention by GH [1]. Hyperglycemia, hypertension, and dyslipidemia have also been reported as adverse effects, but more importantly, a growing number of papers are investigating a potential link between increased incidence of cancer in patients who receive GH, although no solid conclusions have been made so far [6]. Because of the fact that GHD necessitates life-long therapy, certain authors suggest that a quality-of-life questionnaire should be implemented in regular practice, for the purposes of long-term monitoring and design of optimal care [7]. Because of the beneficial effects on the cardiovascular, skeletal and endocrine system, treatment with rhGH is advised even after maximal height and plateau of body growth is reached, but its cost-effectiveness has questioned this type of treatment [4] [6].

When compared to the general population, mortality rates of AO-GHD have shown to be higher, primarily because of cardiovascular and other complications that develop in these patients, but the exact pathophysiological mechanisms that lead to increased mortality rates are not entirely clear [1]. Inappropriate replacement of pituitary hormones other than GH may be one of the reasons, while a presence of concomitant risks and adverse events that occur may also be involved [1]. It is important to mention that almost 50% of children with this condition are left undiagnosed [4], which is why high clinical suspicion toward GHD should be present when evaluating short stature and changes in growth and body composition.

GHD may arise as a result of genetic, but also various acquired conditions [1] [2]:

• Transcription factor defects - mutations in PROP1, POUF-1 and HESX1, factors involved in gene transcription related to GH have shown to be an important cause of GHD [8].
• GH and growth hormone-releasing hormone receptor (GHRH) gene defects - Both autosomal dominant and recessive, but also X-linked modes of inheritance have been described in a literature [2] [3].
• Congenital structural abnormalities such as septooptic dysplasia, empty sella syndrome, encephalocele, and arachnoid cyst.
• Pituitary tumors - Adenoma, craniopharyngioma, glioma/astrocytoma, Rathke's cleft cyst, germinoma, or metastatic disease.
• Perinatal or postnatal trauma - Births in non-cephalic position (especially breech deliveries) have been one of the most common causes of trauma in newborns prior to the introduction of the cesarean section, but GHD due to early trauma is still being reported [2].
• Miscellaneous infiltrative diseases - Tuberculosis, sarcoidosis, and Langerhans cell histiocytosis.

In a small number of cases, the cause remains unknown, in which case the diagnosis of idiopathic GHD is made [1].

In the United Kingdom, GHD has an established incidence rate of 1 in 3,500-4,000 live births, with similar results obtained in the United States (1 in at least 3,480) [4] [9]. AO-GHD appears at an incidence rate between 1.42 and 1.9 per 100,000 individuals in Denmark, while prevalence rates in UK adults are around 1 in 3,000 [4]. Gender predilection toward males has been confirmed in several reports [9] [10].

Under physiological conditions, GH plays an essential role in maintaining normal body composition, primarily muscle mass, and percentage of adipose tissue [1]. Decreased glucose uptake and accelerated protein synthesis are induced in muscular tissue by GH, whereas cardiovascular effects include an increase in myocardial mass, cardiac output and increase in exercise capacity [4]. Because of GH deficiency, a significant decrease in lean body mass and total body water occurs, leading to an increase in fat content [1], while a low rate of bone mineralization leads to osteopenia and reduced bone mineral density [1]. An inability of the cardiovascular system to grow at desired rate occurs and is the reason why fatigue and the quality of life in general, is affected [4]. Apart from the apparent effects of GH on body composition, its role in an induction of inflammatory parameters (including CRP and IL-6) has been documented as well [1], leading to the assumption that GH also plays an important role in functioning of the immune system.

Unfortunately, it is not possible to prevent GHD, but an early diagnosis and identification of the underlying cause may significantly reduce the burden of the disease and provide a better quality of life.

Growth hormone deficiency (GHD) is a disorder that develops as a part of numerous conditions that involve the pituitary gland and cause insufficient production of growth hormone (GH) [1]. Genetic disorders involving GH and growth hormone-releasing hormone (GHRH) receptors, congenital abnormalities such as encephalocele, empty sella syndrome and septooptic dysplasia, endocranial tumors (adenoma, craniopharyngioma, or metastatic disease) and perinatal/postnatal trauma are some of the conditions that may interfere with production and activity of GH [1] [2]. Epidemiology studies show that the incidence rates of GHD vary between 1 in 4,000-10,000 live births and a significant predilection toward males is detected [3]. Under physiological conditions, GH is responsible for achieving adequate bone mass, lean body mass, and overall tissue growth, which is why the clinical presentation universally includes growth retardation and short stature [3]. Depending on the underlying cause, the onset of symptoms may be in childhood or in adulthood and the terms childhood-onset GHD (CO-GHD) and adult-onset GHD (AO-GHD) are frequently used in literature to distinguish the two forms [4]. Additional signs include increased obesity and neurological deficits that may suggest the underlying cause (bitemporal hemianopsia in the setting of a pituitary adenoma or anosmia due to a presence of a craniopharyngioma), but a thorough diagnostic evaluation is necessary to confirm GHD as a cause of symptoms. Dyslipidemia, impaired glucose metabolism and disturbances of other pituitary hormones, such as thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), luteinizing hormone (LH) and follicular stimulating hormone (FSH) may be detected too, as studies have shown that GH abnormalities are present in almost 100% of cases when 3 or more pituitary hormones are disturbed [5]. Magnetic resonance imaging (MRI) of the endocranium is an important imaging procedure that may identify the lesion responsible for GHD, but to confirm the diagnosis, GH stimulation test should be performed [1]. Despite being the gold standard in these patients, it requires a rigorous preparation under close supervision, which is why GH-releasing peptide-2 (GHRP-2) test and measurements of insulin-growth factor 1 (IGF-1) are often done instead because they are safe and more easily performed [1] [3]. The mainstay of treatment is supplementation with recombinant human GH (rhGH) in a carefully designed regimen and life-long therapy may be recommended due to a prevention of adverse effects that may occur later in life (osteopenia, dyslipidemia, and other metabolic changes). The issue of cost-effectiveness, however, has emerged as an issue in clinical practice [6]. GHD has shown to affect the quality of life of many patients [7], making long-term care and evaluation mandatory in ensuring good patient outcomes.

Maintenance of proper body composition and adequate growth are the main functions of growth hormone (GH), which is synthesized in the hypophysis (also known as the pituitary gland) and numerous conditions may impair its activity in the body or its production. Growth hormone deficiency (GHD) is a clinical entity that is defined as markedly reduced activity of GH in the body, leading to growth retardation and symptoms such as accumulation of fat and reduction in muscle mass. Other findings include a reduced bone mass that may be a risk for fractures, as well as various neurological symptoms, depending on the underlying cause. Brain tumors, genetic diseases that affect GH receptors, trauma experienced in pregnancy or during delivery and various congenital defects may all be responsible for an insufficient synthesis of GH. It is estimated that 1 in 4,000-10,000 individuals develops GHD due to any cause and a significant predilection toward males is established. To make an initial diagnosis, it is essential to perform a thorough workup consisting of laboratory studies that may reveal changes in lipid levels, altered glucose concentrations and derangement of other pituitary hormones, together with imaging studies of the brain in the form of magnetic resonance imaging (MRI), which may point to the underlying cause. To confirm GHD, however, GH-stimulation test is considered to be the most reliable diagnostic method and consists of serial blood sampling in a matter of several hours after use of various drugs. But because it is contraindicated in patients suffering from seizures and heart disease and the fact that it may cause serious adverse effects, alternative and safer methods of evaluation are more frequently performed, including measurement of insulin-growth factor 1 (IGF-1) and GH-releasing peptide-2 (GHRP-2) test. Treatment principles rely on supplementation with recombinant human GH (rhGH) and the regimen depends on the patient's age, gender, a presence of comorbidities and current drug use. The beneficial effects of prolonged rhGH supplementation on the musculoskeletal and cardiovascular system have been brought into question by a very large cost of treatment, while certain studies are pointing to an increased risk of malignancy when using GH as a therapeutic measure. Because GHD may severely impact the overall quality of life of the patient, long-term monitoring, and care are necessary to provide optimal therapy.

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