Browsing by Author "Pekic, Sandra (6602553641)"

We report here the case of a 21-year-old woman with a large sellar tumor, extending to the suprasellar area associated with growth hormone deficiency, hypogonadism, hypocorticism, and hyperprolactinemia. Transsphenoidal surgery was performed, and histologic, immunohistochemical, and electron microscopic study lead to the diagnosis of granular cell tumor. These tumors are, in most cases, very small and are found incidentally at autopsy of older patients. Our case is exceptional because the tumor developed in a young woman, extended to the suprasellar region, and caused clinical symptoms. © Humana Press Inc. 2007.

We report here the case of a 21-year-old woman with a large sellar tumor, extending to the suprasellar area associated with growth hormone deficiency, hypogonadism, hypocorticism, and hyperprolactinemia. Transsphenoidal surgery was performed, and histologic, immunohistochemical, and electron microscopic study lead to the diagnosis of granular cell tumor. These tumors are, in most cases, very small and are found incidentally at autopsy of older patients. Our case is exceptional because the tumor developed in a young woman, extended to the suprasellar region, and caused clinical symptoms. © Humana Press Inc. 2007.

Hypopituitarism often remains unrecognized due to subtle clinical manifestations. Anterior pituitary hormone deficiencies may present as isolated or multiple and may be transient or permanent. Traumatic brain injury (TBI) is recognized as a risk factor for hypopituitarism, most frequently presenting with isolated growth hormone deficiency (GHD). Data analysis shows that about 15% of patients with TBI have some degree of hypopituitarism which if not recognized may be mistakenly ascribed to persistent neurologic injury and cognitive impairment. Identification of predictors for hypopituitarism after TBI is important, one of them being the severity of TBI. The mechanisms involve lesions in the hypothalamic-pituitary axis and inflammatory changes in the central nervous system (CNS). With time, hypopituitarism after TBI may progress or reverse. Cranial irradiation is another important risk factor for hypopituitarism. Deficiencies in anterior pituitary hormone secretion (partial or complete) occur following radiation damage to the hypothalamic-pituitary region, the severity and frequency of which correlate with the total radiation dose delivered to the region and the length of follow-up. These radiation-induced hormone deficiencies are irreversible and progressive. Despite numerous case reports, the incidence of hypothalamic-pituitary dysfunction following infectious diseases of the CNS has been underestimated. Hypopituitarism usually relates to the severity of the disease, type of causative agent (bacterial, TBC, fungal, or viral) and primary localization of the infection. Unrecognized hypopituitarism may be misdiagnosed as postencephalitic syndrome, while the presence of a sellar mass with suprasellar extension may be misdiagnosed as pituitary macroadenoma in a patient with pituitary abscess which is potentially a life-threatening disease. © 2014 Elsevier B.V.

Hypopituitarism often remains unrecognized due to subtle clinical manifestations. Anterior pituitary hormone deficiencies may present as isolated or multiple and may be transient or permanent. Traumatic brain injury (TBI) is recognized as a risk factor for hypopituitarism, most frequently presenting with isolated growth hormone deficiency (GHD). Data analysis shows that about 15% of patients with TBI have some degree of hypopituitarism which if not recognized may be mistakenly ascribed to persistent neurologic injury and cognitive impairment. Identification of predictors for hypopituitarism after TBI is important, one of them being the severity of TBI. The mechanisms involve lesions in the hypothalamic-pituitary axis and inflammatory changes in the central nervous system (CNS). With time, hypopituitarism after TBI may progress or reverse. Cranial irradiation is another important risk factor for hypopituitarism. Deficiencies in anterior pituitary hormone secretion (partial or complete) occur following radiation damage to the hypothalamic-pituitary region, the severity and frequency of which correlate with the total radiation dose delivered to the region and the length of follow-up. These radiation-induced hormone deficiencies are irreversible and progressive. Despite numerous case reports, the incidence of hypothalamic-pituitary dysfunction following infectious diseases of the CNS has been underestimated. Hypopituitarism usually relates to the severity of the disease, type of causative agent (bacterial, TBC, fungal, or viral) and primary localization of the infection. Unrecognized hypopituitarism may be misdiagnosed as postencephalitic syndrome, while the presence of a sellar mass with suprasellar extension may be misdiagnosed as pituitary macroadenoma in a patient with pituitary abscess which is potentially a life-threatening disease. © 2014 Elsevier B.V.

Background: Prolactin-raising antipsychotics, risperidone (antidopaminergic activity), may be associated with low bone mass. On the other hand, risperidone may cause an increase in body weight thought to be favorable for bone. Objectives: (1) To determine bone remodeling parameters and bone mass in patients with schizophrenia on long-term treatment with long-acting injectable risperidone (LAIR) in naturalistic settings, and (2) to evaluate the change in body weight, metabolic profile and neuroendocrine status in these patients. Design: This was a prospective, cross-sectional study. Patients: Patients included 26 outpatients with controlled schizophrenia in real-life conditions (age 31.3 ± 1.3 years, BMI 28.1 ± 1.0) on long-term maintenance therapy with LAIR for a mean of 18.0 ± 1.6 months (range 6-36) with a mean dose of 38 ± 2 mg. 35 subjects matched for sex, age, BMI and education served as healthy controls. Methods: Serum osteocalcin, C-terminal telopeptide of type I collagen (CTx), vitamin D, leptin, prolactin, sex steroids, and parathyroid hormone were assessed. Indices of insulin sensitivity and resistance were determined following an oral glucose tolerance test (OGTT). Bone mineral density (BMD) was measured by dual X-ray absorptiometry at the lumbar spine (LS) and femoral neck (FN). Results: Mild to moderate hyperprolactinemia (1,000-2,000 mU/l) was associated with asymptomatic hypogonadism. Prolactin values >2,000 mU/l occurred in a few female patients. Hypogonadism leads to a slight increase (upper limit of normal) in bone resorption marker (CTx) in patients with schizophrenia (p = 0.023). As for bone mass, although lower at the spine than in healthy subjects, it did not reach statistical significance (p = 0.094), while at the FN, BMD was not different from healthy subjects. Body weight increased on average 8.7 ± 1.6 kg in more than 50% of patients. Leptin levels adjusted for BMI in females were significantly higher in patients than in healthy female subjects (p = 0.018), while in males there was no difference between the groups (p = 0.833). A high prevalence of low vitamin D levels and more current smokers were found in patients with schizophrenia. As for the metabolic profile during treatment with risperidone, the low Matsuda index of insulin sensitivity (p = 0.039) confirmed insulin resistance in these patients. Conclusion: A potential long-term consequence of asymptomatic hypogonadism due to risperidone-induced hyperprolactinemia might cause a slight rise in bone resorption marker (CTx). On the other hand, by increasing body weight, risperidone could have a protective effect on the bone and thus no change in bone mass was recorded when compared with healthy controls. © 2011 S. Karger AG, Basel.

Background: Prolactin-raising antipsychotics, risperidone (antidopaminergic activity), may be associated with low bone mass. On the other hand, risperidone may cause an increase in body weight thought to be favorable for bone. Objectives: (1) To determine bone remodeling parameters and bone mass in patients with schizophrenia on long-term treatment with long-acting injectable risperidone (LAIR) in naturalistic settings, and (2) to evaluate the change in body weight, metabolic profile and neuroendocrine status in these patients. Design: This was a prospective, cross-sectional study. Patients: Patients included 26 outpatients with controlled schizophrenia in real-life conditions (age 31.3 ± 1.3 years, BMI 28.1 ± 1.0) on long-term maintenance therapy with LAIR for a mean of 18.0 ± 1.6 months (range 6-36) with a mean dose of 38 ± 2 mg. 35 subjects matched for sex, age, BMI and education served as healthy controls. Methods: Serum osteocalcin, C-terminal telopeptide of type I collagen (CTx), vitamin D, leptin, prolactin, sex steroids, and parathyroid hormone were assessed. Indices of insulin sensitivity and resistance were determined following an oral glucose tolerance test (OGTT). Bone mineral density (BMD) was measured by dual X-ray absorptiometry at the lumbar spine (LS) and femoral neck (FN). Results: Mild to moderate hyperprolactinemia (1,000-2,000 mU/l) was associated with asymptomatic hypogonadism. Prolactin values >2,000 mU/l occurred in a few female patients. Hypogonadism leads to a slight increase (upper limit of normal) in bone resorption marker (CTx) in patients with schizophrenia (p = 0.023). As for bone mass, although lower at the spine than in healthy subjects, it did not reach statistical significance (p = 0.094), while at the FN, BMD was not different from healthy subjects. Body weight increased on average 8.7 ± 1.6 kg in more than 50% of patients. Leptin levels adjusted for BMI in females were significantly higher in patients than in healthy female subjects (p = 0.018), while in males there was no difference between the groups (p = 0.833). A high prevalence of low vitamin D levels and more current smokers were found in patients with schizophrenia. As for the metabolic profile during treatment with risperidone, the low Matsuda index of insulin sensitivity (p = 0.039) confirmed insulin resistance in these patients. Conclusion: A potential long-term consequence of asymptomatic hypogonadism due to risperidone-induced hyperprolactinemia might cause a slight rise in bone resorption marker (CTx). On the other hand, by increasing body weight, risperidone could have a protective effect on the bone and thus no change in bone mass was recorded when compared with healthy controls. © 2011 S. Karger AG, Basel.

In familial cases of combined pituitary hormone deficiency the most common mutations are that of Prophet of Pit 1 (PROP1) gene. PROP1 mutations are associated with deficiencies of growth hormone, thyrotropin, prolactin, and gonadotropins (follicle-stimulating hormone and luteinizing hormone), with evolving adrenocorticotropin (ACTH) deficiency in some cases. On imaging in most patients the pituitary gland is hypoplastic, but occasionally transient pituitary enlargement is found. We report a 22-year-old female initially diagnosed at age 12 with familial hypopituitarism due to PROP1 mutation, who presented with coma and respiratory arrest (acute hyponatremia). She was urgently treated in Intensive Care Unit of Emergency Center with hypertonic saline and stress doses of hydrocortisone, which resulted in the fast increase of plasma osmolality resulting in the osmotic demyelination syndrome. Simultaneously and incidentally on computed tomography scan a large sellar and suprasellar mass were reported as possible Rathke's cleft cyst or craniopharyngioma. Once the patient was stable, ACTH deficiency was documented. She remained replaced with hydrocortisone and subsequently underwent transphenoidal surgery. The removed sellar content revealed no pituitary adenoma or pituitary cells, but only an eosinophilic, colloid- like mass, and necrotic acellular debris. Her sister with hypopituitarism had an empty sella. Genetic testing in both sisters revealed the same homozygous c.150delA mutation in PROP1 gene. Here we report two sisters with the same PROP1 mutation who presented in adulthood with different pituitary morphology, one of them with a large sellar and suprasellar mass, in which transphenoidal surgery provided an extremely rare opportunity for a histopathological analysis of the sellar content. Due to the lack of endocrine care during the transition period hypocortisolism which evolved, a consequence of PROP1 mutation, was not recognized. Empirical use of hydrocortisone in the Intensive Care in our patient with life-threatening acute hyponatremia was appropriate but because glucocorticoid therapy on its own corrects hyponatremia even after stopping hypertonic saline infusion, the risk for over-correction of hyponatremia in ACTH deficiency is high. © Springer Science+Business Media, LLC 2011.

In familial cases of combined pituitary hormone deficiency the most common mutations are that of Prophet of Pit 1 (PROP1) gene. PROP1 mutations are associated with deficiencies of growth hormone, thyrotropin, prolactin, and gonadotropins (follicle-stimulating hormone and luteinizing hormone), with evolving adrenocorticotropin (ACTH) deficiency in some cases. On imaging in most patients the pituitary gland is hypoplastic, but occasionally transient pituitary enlargement is found. We report a 22-year-old female initially diagnosed at age 12 with familial hypopituitarism due to PROP1 mutation, who presented with coma and respiratory arrest (acute hyponatremia). She was urgently treated in Intensive Care Unit of Emergency Center with hypertonic saline and stress doses of hydrocortisone, which resulted in the fast increase of plasma osmolality resulting in the osmotic demyelination syndrome. Simultaneously and incidentally on computed tomography scan a large sellar and suprasellar mass were reported as possible Rathke's cleft cyst or craniopharyngioma. Once the patient was stable, ACTH deficiency was documented. She remained replaced with hydrocortisone and subsequently underwent transphenoidal surgery. The removed sellar content revealed no pituitary adenoma or pituitary cells, but only an eosinophilic, colloid- like mass, and necrotic acellular debris. Her sister with hypopituitarism had an empty sella. Genetic testing in both sisters revealed the same homozygous c.150delA mutation in PROP1 gene. Here we report two sisters with the same PROP1 mutation who presented in adulthood with different pituitary morphology, one of them with a large sellar and suprasellar mass, in which transphenoidal surgery provided an extremely rare opportunity for a histopathological analysis of the sellar content. Due to the lack of endocrine care during the transition period hypocortisolism which evolved, a consequence of PROP1 mutation, was not recognized. Empirical use of hydrocortisone in the Intensive Care in our patient with life-threatening acute hyponatremia was appropriate but because glucocorticoid therapy on its own corrects hyponatremia even after stopping hypertonic saline infusion, the risk for over-correction of hyponatremia in ACTH deficiency is high. © Springer Science+Business Media, LLC 2011.

In recent years fungi are favoured as origin of chronic rhinosinusitis (CRS), especially with nasal polyps (wNP). Sensitive methods for fungal detection are still absent, therefore we used NP tissue single-cell suspension for mycology investigations in patients with recalcitrant NP (rNP) that underwent functional endoscopic sinus surgery (FESS). A prospective case-series study and culture-based mycological examination were conducted in patients who underwent FESS for the first time (ft-FESS) and those with repeated FESS (re-FESS). The study was conducted in a tertiary Otorhinolaryngology Unit of Clinical Centre of Serbia. A total of 43 consecutive patients with CRSwNP underwent FESS. Culture-based mycological examination of single-cell suspension was done on 55 NPs samples. Patient’s co-morbidity data were collected. Repeated FESS was observed in 19/43 (44 %) patients (re-FESS group). Asthma and aspirin intolerance were more frequent in re-FESS than in ft-FESS group (p = 0.000, p = 0.002; respectively). Fungi were detected (wF) in 10/43 (23.3 %) patients (FESSwF group), representing 13/55 culture positive NP tissue (23.6 %). Fungal presence was higher in re-FESS than in ft-FESS group (42 and 8 %, respectively; p = 0.01). Significantly longer duration of CRS was observed in FESSwF than in fungal negative patients (p = 0.033). Predominate strain was Aspergillus flavus detected in 6/10 patients. This is the first study which analysed association of fungi in single-cell suspension of NP tissue and rNP. We demonstrate significantly higher percentage of positive fungal finding in re-FESSwF than in ft-FESSwF group. The most commonly isolated species in our patients was A. flavus. © 2015, Springer-Verlag Berlin Heidelberg.

Background: Aryl hydrocarbon receptor-interacting protein (AIP) is evolutionarily conserved and expressed widely throughout the organism. Loss-of-function AIP mutations predispose to young-onset pituitary adenomas. AIP co-localizes with growth hormone in normal and tumorous somatotroph secretory vesicles. AIP protein is detectable in circulation. We aimed to investigate possible AIP and GH co-secretion, by studying serum AIP and GH levels at baseline and after GH stimulation or suppression, in GH deficiency (GHD) and in acromegaly patients. Subjects and methods: Insulin tolerance test (ITT) was performed in GHD patients (n = 13) and age-BMI-matched normal GH axis control patients (n = 31). Oral glucose tolerance test (OGTT) was performed in active acromegaly patients (n = 26) and age-BMI-matched normal GH axis control patients (n = 18). In-house immunometric assay was developed for measuring circulating AIP. Results: Serum AIP levels were in the 0.1 ng/mL range independently of gender, age or BMI. Baseline AIP did not differ between GHD and non-GHD or between acromegaly and patients with no acromegaly. There was no change in peak, trough or area under the curve during OGTT or ITT. Serum AIP did not correlate with GH during ITT or OGTT. Conclusions: Human circulating serum AIP in vivo was assessed by a novel immunometric assay. AIP levels were independent of age, sex or BMI and unaffected by hypoglycaemia or hyperglycaemia. Despite co-localization in secretory vesicles, AIP and GH did not correlate at baseline or during GH stimulation or suppression tests. A platform of reliable serum AIP measurement is established for further research of its circulatory source, role and impact. © 2019 The authors

Background: Aryl hydrocarbon receptor-interacting protein (AIP) is evolutionarily conserved and expressed widely throughout the organism. Loss-of-function AIP mutations predispose to young-onset pituitary adenomas. AIP co-localizes with growth hormone in normal and tumorous somatotroph secretory vesicles. AIP protein is detectable in circulation. We aimed to investigate possible AIP and GH co-secretion, by studying serum AIP and GH levels at baseline and after GH stimulation or suppression, in GH deficiency (GHD) and in acromegaly patients. Subjects and methods: Insulin tolerance test (ITT) was performed in GHD patients (n = 13) and age-BMI-matched normal GH axis control patients (n = 31). Oral glucose tolerance test (OGTT) was performed in active acromegaly patients (n = 26) and age-BMI-matched normal GH axis control patients (n = 18). In-house immunometric assay was developed for measuring circulating AIP. Results: Serum AIP levels were in the 0.1 ng/mL range independently of gender, age or BMI. Baseline AIP did not differ between GHD and non-GHD or between acromegaly and patients with no acromegaly. There was no change in peak, trough or area under the curve during OGTT or ITT. Serum AIP did not correlate with GH during ITT or OGTT. Conclusions: Human circulating serum AIP in vivo was assessed by a novel immunometric assay. AIP levels were independent of age, sex or BMI and unaffected by hypoglycaemia or hyperglycaemia. Despite co-localization in secretory vesicles, AIP and GH did not correlate at baseline or during GH stimulation or suppression tests. A platform of reliable serum AIP measurement is established for further research of its circulatory source, role and impact. © 2019 The authors

Background: Intracranial germinomas (ICG) are uncommon brain neoplasms with extremely rare familial occurrence. Because ICG invades the hypothalamus and/or pituitary, endocrine dysfunction is one of the common determinants of these tumours. We present two brothers with a history of ICG. Patient 1 is a 25-year-old male who suffered from weakness of the right half of his body at the age of 18 years. Cranial MRI revealed a mass lesion in the left thalamus. He underwent neurosurgery, and the tumour was removed completely. Histopathological (HP) and immunohistochemical analyses verified the diagnosis of pure germinoma. He experienced complete remission of the tumour after radiation therapy. At the age of 22 years a diagnosis of isolated growth hormone deficiency (IGHD) was established and GH replacement was initiated. Molecular genetic analysis of the tumour tissue detected the mutation within exon 2 in KRAS gene. Patient 2 is a 20-year-old man who presented with diabetes insipidus at the age of 12 years. MRI detected tumour in the third ventricle and pineal region. After endoscopic tumour biopsy the HP diagnosis was pure germinoma. He received chemotherapy followed by radiotherapy and was treated with GH during childhood. At the age of 18 years GH replacement was reintroduced. A six-month follow-up during the subsequent two years in both brothers demonstrated the IGF1 normalisation with no MRI signs of tumour recurrence. Conclusion: To the best of our knowledge, so far only six reports have been published related to familial ICG. The presented two brothers are the first report of familial ICG case outside Japan. They have been treated successfully with GH therapy in adulthood. © 2018 Via Medica. All rights reserved.

Background: Intracranial germinomas (ICG) are uncommon brain neoplasms with extremely rare familial occurrence. Because ICG invades the hypothalamus and/or pituitary, endocrine dysfunction is one of the common determinants of these tumours. We present two brothers with a history of ICG. Patient 1 is a 25-year-old male who suffered from weakness of the right half of his body at the age of 18 years. Cranial MRI revealed a mass lesion in the left thalamus. He underwent neurosurgery, and the tumour was removed completely. Histopathological (HP) and immunohistochemical analyses verified the diagnosis of pure germinoma. He experienced complete remission of the tumour after radiation therapy. At the age of 22 years a diagnosis of isolated growth hormone deficiency (IGHD) was established and GH replacement was initiated. Molecular genetic analysis of the tumour tissue detected the mutation within exon 2 in KRAS gene. Patient 2 is a 20-year-old man who presented with diabetes insipidus at the age of 12 years. MRI detected tumour in the third ventricle and pineal region. After endoscopic tumour biopsy the HP diagnosis was pure germinoma. He received chemotherapy followed by radiotherapy and was treated with GH during childhood. At the age of 18 years GH replacement was reintroduced. A six-month follow-up during the subsequent two years in both brothers demonstrated the IGF1 normalisation with no MRI signs of tumour recurrence. Conclusion: To the best of our knowledge, so far only six reports have been published related to familial ICG. The presented two brothers are the first report of familial ICG case outside Japan. They have been treated successfully with GH therapy in adulthood. © 2018 Via Medica. All rights reserved.

Context: Congenital hypopituitarism is a syndrome which is associated with single or multiple pituitary hormone deficiencies. Mutations in a number of developmental genes have been linked to combined pituitary hormone deficiencies, the most common being mutation in the pituitary homeobox protein prophet of the Pit 1 gene (PROP1). PROP1 exhibits DNA-binding and transcriptional activities. On magnetic resonance imaging, most patients with PROP1 mutation have a hypoplastic pituitary gland. Occasionally, transient pituitary enlargement before definite involution is reported. Kallmann syndrome (KS) is a human developmental genetic disorder which is a clinically (isolated hypogonadotropic hypogonadism-IHH) and genetically heterogeneous disease. Routine neuroimaging in classical IHH is thought to be of limited clinical value and normal anatomy of the hypothalamic-pituitary region is often reported. For neither disorder are there many reports on imaging during adulthood. Nor are there any guidelines concerning long-term imaging follow-up in patients with developmental pituitary disorders. Objective: Our aim was to present unusual endocrine and imaging abnormalities which developed in adulthood in two patients with developmental pituitary disorders. Cases: We report a female with combined pituitary hormone deficiencies (GH, TSH, gonadotropin and ACTH), except for prolactin, as a consequence of PROP1 mutation, and a male with KS (anosmia and IHH) due to Kal 2 gene (fibroblast growth factor receptor 1- FGFR1) mutation, both of whom in adulthood presented with prolactinomas. CONCLUSION: Both patients with developmental gene mutations, after long-term correction of their sex steroid status, developed prolactinomas. Although the exact mechanism of pituitary tumorigenesis is not known, we speculate that sex steroids may have facilitated prolactinoma development from the prolactin cell pool which underwent uncontrolled proliferation in the setting of a developmental disorder.

Objective: Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) represent rare and common forms of GnRH deficiency, respectively. Both CDGP and CHH present with delayed puberty, and the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while the genetic basis of CDGP is poorly understood. Design: We characterized and compared the genetic architectures of CHH and CDGP, to test the hypothesis of a shared genetic basis between these disorders. Methods: Exome sequencing data were used to identify rare variants in known genes in CHH (n = 116), CDGP (n = 72) and control cohorts (n = 36 874 ExAC and n = 405 CoLaus). Results: Mutations in at least one CHH gene were found in 51% of CHH probands, which is significantly higher than in CDGP (7%, P = 7.6 × 10-11) or controls (18%, P = 5.5 × 10-12). Similarly, oligogenicity (defined as mutations in more than one gene) was common in CHH patients (15%) relative to CDGP (1.4%, P = 0.002) and controls (2%, P = 6.4 × 10-7). Conclusions: Our data suggest that CDGP and CHH have distinct genetic profiles, and this finding may facilitate the differential diagnosis in patients presenting with delayed puberty. © 2018 The authors.

Objective: Congenital hypogonadotropic hypogonadism (CHH) and constitutional delay of growth and puberty (CDGP) represent rare and common forms of GnRH deficiency, respectively. Both CDGP and CHH present with delayed puberty, and the distinction between these two entities during early adolescence is challenging. More than 30 genes have been implicated in CHH, while the genetic basis of CDGP is poorly understood. Design: We characterized and compared the genetic architectures of CHH and CDGP, to test the hypothesis of a shared genetic basis between these disorders. Methods: Exome sequencing data were used to identify rare variants in known genes in CHH (n = 116), CDGP (n = 72) and control cohorts (n = 36 874 ExAC and n = 405 CoLaus). Results: Mutations in at least one CHH gene were found in 51% of CHH probands, which is significantly higher than in CDGP (7%, P = 7.6 × 10-11) or controls (18%, P = 5.5 × 10-12). Similarly, oligogenicity (defined as mutations in more than one gene) was common in CHH patients (15%) relative to CDGP (1.4%, P = 0.002) and controls (2%, P = 6.4 × 10-7). Conclusions: Our data suggest that CDGP and CHH have distinct genetic profiles, and this finding may facilitate the differential diagnosis in patients presenting with delayed puberty. © 2018 The authors.

Growth hormone (GH) replacement in GH deficient (GHD) children secures normal linear growth, while in GHD adults it improves metabolic status, body composition and quality of life. Safety of GH treatment is an important issue in particular concerning the controversy of potential cancer risk. Unlike in congenital IGF-1 deficiency, there is no complete protection against cancer in GHD patients. Important modifiable risk factors in GHD patients are obesity, insulin resistance, sedentary behavior, circadian rhythm disruption, chronic low grade inflammation and concomitant sex hormone replacement. Age, family history, hereditary cancer predisposition syndromes or cranial irradiation may present non-modifiable risk factors. Quantifying the risk of cancer in relation to GH therapy in adult GHD patients is complex. There is evidence that links GH to cancer occurrence or promotion, but the evidence is progressively weaker when moving from in vitro studies to in vivo animal studies to epidemiological studies and finally to studies on GH treated patients. GH-IGF inhibition in experimental animals leads to decreased cancer incidence and progression. Epidemiological studies suggest an association of high normal circulating IGF-1 or GH to cancer incidence in general population. Data regarding cancer incidence in acromegaly are inconsistent but thyroid and colorectal neoplasias are the main source of concern. Replacement therapy with rhGH for GHD is generally safe. Overall the rate of de novo cancers was not increased in studies of GH-treated GHD patients. Additional caution is mandated in patients with history of cancer, strong family history of cancer and with advancing age. Childhood cancer survivors may be at increased risk for secondary neoplasms compared with general population. In this subgroup GH therapy should be used cautiously and with respect to other risk factors (cranial irradiation etc). We believe that the benefits of GH therapy against the morbidity of untreated GH deficiency outweigh the theoretical cancer risk. Proper monitoring of GH treatment with diligent cancer surveillance remains essential. © 2017 Elsevier Ltd

Growth hormone (GH) replacement in GH deficient (GHD) children secures normal linear growth, while in GHD adults it improves metabolic status, body composition and quality of life. Safety of GH treatment is an important issue in particular concerning the controversy of potential cancer risk. Unlike in congenital IGF-1 deficiency, there is no complete protection against cancer in GHD patients. Important modifiable risk factors in GHD patients are obesity, insulin resistance, sedentary behavior, circadian rhythm disruption, chronic low grade inflammation and concomitant sex hormone replacement. Age, family history, hereditary cancer predisposition syndromes or cranial irradiation may present non-modifiable risk factors. Quantifying the risk of cancer in relation to GH therapy in adult GHD patients is complex. There is evidence that links GH to cancer occurrence or promotion, but the evidence is progressively weaker when moving from in vitro studies to in vivo animal studies to epidemiological studies and finally to studies on GH treated patients. GH-IGF inhibition in experimental animals leads to decreased cancer incidence and progression. Epidemiological studies suggest an association of high normal circulating IGF-1 or GH to cancer incidence in general population. Data regarding cancer incidence in acromegaly are inconsistent but thyroid and colorectal neoplasias are the main source of concern. Replacement therapy with rhGH for GHD is generally safe. Overall the rate of de novo cancers was not increased in studies of GH-treated GHD patients. Additional caution is mandated in patients with history of cancer, strong family history of cancer and with advancing age. Childhood cancer survivors may be at increased risk for secondary neoplasms compared with general population. In this subgroup GH therapy should be used cautiously and with respect to other risk factors (cranial irradiation etc). We believe that the benefits of GH therapy against the morbidity of untreated GH deficiency outweigh the theoretical cancer risk. Proper monitoring of GH treatment with diligent cancer surveillance remains essential. © 2017 Elsevier Ltd

Hypopituitarism is defined as one or more pituitary hormone deficits due to a lesion in the hypothalamic-pituitary region. By far, the most common cause of hypopituitarism associated with a sellar mass is a pituitary adenoma. A high index of suspicion is required for diagnosing hypopituitarism in several other conditions such as other massess in the sellar and parasellar region, brain damage caused by radiation and by traumatic brain injury, vascular lesions, infiltrative/immunological/inflammatory diseases (lymphocytic hypophysitis, sarcoidosis and hemochromatosis), infectious diseases and genetic disorders. Hypopituitarism may be permanent and progressive with sequential pattern of hormone deficiencies (radiation-induced hypopituitarism) or transient after traumatic brain injury with possible recovery occurring years from the initial event. In recent years, there is increased reporting of less common and less reported causes of hypopituitarism with its delayed diagnosis. The aim of this review is to summarize the published data and to allow earlier identification of populations at risk of hypopituitarism as optimal hormonal replacement may significantly improve their quality of life and life expectancy. © 2017 European Society of Endocrinology Printed in Great Britain.

Hypopituitarism is defined as one or more pituitary hormone deficits due to a lesion in the hypothalamic-pituitary region. By far, the most common cause of hypopituitarism associated with a sellar mass is a pituitary adenoma. A high index of suspicion is required for diagnosing hypopituitarism in several other conditions such as other massess in the sellar and parasellar region, brain damage caused by radiation and by traumatic brain injury, vascular lesions, infiltrative/immunological/inflammatory diseases (lymphocytic hypophysitis, sarcoidosis and hemochromatosis), infectious diseases and genetic disorders. Hypopituitarism may be permanent and progressive with sequential pattern of hormone deficiencies (radiation-induced hypopituitarism) or transient after traumatic brain injury with possible recovery occurring years from the initial event. In recent years, there is increased reporting of less common and less reported causes of hypopituitarism with its delayed diagnosis. The aim of this review is to summarize the published data and to allow earlier identification of populations at risk of hypopituitarism as optimal hormonal replacement may significantly improve their quality of life and life expectancy. © 2017 European Society of Endocrinology Printed in Great Britain.