Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Jan 13, 2016
The cyclic adenosine monophosphate (cAMP) intracellular signaling pathway mediates the physiologi... more The cyclic adenosine monophosphate (cAMP) intracellular signaling pathway mediates the physiological effects of several hormones and neurotransmitters, acting by the activation of G-protein coupled receptors (GPCRs) and several downstream intracellular effectors, including the heterotrimeric stimulatory G-protein (Gs), the cAMP-dependent protein kinase A (PKA) and cAMP-specific phosphodiesterases (PDEs). Defective G protein-mediated signaling has been associated to an increasing number of disorders, including Albright hereditary osteodistrophy (AHO) and pseudohypoparathyroidism (PHP), a heterogeneous group of rare genetic metabolic disorders due to molecular defects at the GNAS locus. Moreover, mutations in PRKAR1A and PDE4D genes have been recently detected in patients with acrodysostosis (ACRDYS), showing a skeletal and endocrinological phenotype partially overlapping with AHO/PHP. Despite the high detection rate of molecular defects by currently available molecular approaches, ab...
Most of the clinical data on the safety profile of desmopressin (DDAVP), which is an effective tr... more Most of the clinical data on the safety profile of desmopressin (DDAVP), which is an effective treatment for both polyuric conditions and bleeding disorders, originate from studies on the tailoring of drug treatment, whereas few reports exist describing severe side effects secondary to drug-drug interaction. We herein describe a case of severe hyponatremia complicated by seizure and coma due to the intake of non-steroidal anti-inflammatory drugs (NSAIDs) in a patient on DDAVP replacement therapy for central diabetes insipidus (DI). A 50-yr-old Caucasian man, with congenital central DI, developed an episode of generalized tonic-clonic seizure, resulting in coma immediately after being admitted to the Emergency Unit for weakness and emesis. Based on his medical history and clinical findings, water intoxication secondary to ketoprofen intake (200 mg/day for the last 3 days) concomitant with DDAVP replacement therapy (Minirin(®) 60 mcg 4 tablets a day) was hypothesized as being the caus...
X-linked acro-gigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplicat... more X-linked acro-gigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and a microduplication in chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in 2 families was dominant with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2-3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight SDS score of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersec...
Acromegaly guidelines updated in 2010 revisited criteria of disease control: if applied, it is li... more Acromegaly guidelines updated in 2010 revisited criteria of disease control: if applied, it is likely that a percentage of patients previously considered as cured might present postglucose GH nadir levels not adequately suppressed, with potential implications on management. This study explored GH secretion, as well as hormonal, clinical, neuroradiological, metabolic, and comorbid profile in a cohort of 40 acromegalic patients considered cured on the basis of the previous guidelines after a mean follow-up period of 17.2 years from remission, in order to assess the impact of the current criteria. At the last follow-up visit, in the presence of normal IGF-I concentrations, postglucose GH nadir was over 0.4 μg/L in 11 patients (Group A) and below 0.4 μg/L in 29 patients (Group B); moreover, Group A showed higher basal GH levels than Group B, whereas a significant decline of both GH and postglucose GH nadir levels during the follow-up was observed in Group B only. No differences in other evaluated parameters were found. These results seem to suggest that acromegalic patients considered cured on the basis of previous guidelines do not need a more intensive monitoring than patients who met the current criteria of disease control, supporting instead that the cut-off of 0.4 mcg/L might be too low for the currently used GH assay.
The diagnosis of hypothalamic-pituitary-adrenal insufficiency (HPAI) is a major clinical challeng... more The diagnosis of hypothalamic-pituitary-adrenal insufficiency (HPAI) is a major clinical challenge. The gold standard procedure remains insulin tolerance test (ITT). This study aimed to evaluate the usefulness of standard-dose corticotrophin stimulation test (SDCT) in diagnosing HPAI. In this prospective study we performed SDCT and ITT in 55 consecutive patients (37F/18M) affected by pituitary disorders. A normal response to ITT was found in 44 patients, while HPAI was diagnosed in 11. Using ITT as reference test, the ROC curve showed that a cortisol value of 18 µg/dl (500 nmol/L) at 30 min or 21.8 µg/dl (600 nmol/L) at 60 min after SDCT represents the best compromise between sensitivity and specificity in diagnosing HPAI. Moreover, 30 min cortisol values >20.3 µg/dl (560 nmol/L) or 60 min cortisol values >24.1 µg/dl (665 nmol/L) exclude HPAI. Four out of 15 patients of Group A, previously non-respondent to SDCT, showed a normal response to a second SDCT. SDCT is not a reliable tool to identify HPAI, but it appears to be more useful in confirming the normality of HPA function. When SDCT fails to exclude HPAI, ITT should be performed. If ITT is contraindicated, retesting patients by SDCT is useful before starting an unnecessary replacement therapy.
A highly polymorphic Cytosine-Adenosine (CA) repeat sequence microsatellite has been identified i... more A highly polymorphic Cytosine-Adenosine (CA) repeat sequence microsatellite has been identified in the promoter region of IGF1 gene. Several studies investigated the relationship between IGF1-(CA)n polymorphism and IGF1 levels, with conflicting results. Aim of this study was to investigate the influence of this polymorphism on clinical and biochemical characteristics of acromegalic patients. Eighty-eight acromegalic patients and 104 normal subjects were included in the study. Blood DNA was extracted and analysed by microsatellite technique using capillary electrophoresis. Patients and controls were subdivided in 19/19 [homozygous for the (CA)19 allele], 19/X [heterozygous for the (CA)19 allele] and X/X (any other genotype). The genotype frequency was significantly different between patients and controls, the proportion of 19/19 being lower (28·4% vs. 50·0%) and 19/X and X/X higher in acromegalic patients than in controls (P = 0·004). There were no significant differences in age, gender, basal and nadir GH, IGF1-SDS, tumour size, metabolic parameters, outcome and treatment among the three groups. The different frequency of genotypes in acromegalic patients vs. controls, as well as the lack of relationship between IGF1-(CA)n polymorphism and clinical and biochemical data in acromegalic patients, was confirmed using an additional alternative genotyping considering (CA)19 and (CA)20 homozygotes and heterozygotes vs. alleles with more than 19 of 20 repeats or less. Our results do not support the hypothesis that IGF-(CA)n alleles may have a significant role in determining clinical, biochemical and outcome of patients with acromegaly. The possible role of IGF1 polymorphism on susceptibility to acromegaly remains to be investigated.
ABSTRACT Transsphenoidal (TNS) surgery remains the primary therapeutic option for GH-secreting pi... more ABSTRACT Transsphenoidal (TNS) surgery remains the primary therapeutic option for GH-secreting pituitary adenomas. The aims of this study were to verify the impact of TNS surgery on treatment of acromegaly before and after identification by a dedicated neurosurgical team and to enumerate diagnostic features of the disease described over three decades. 41 patients (group A) who underwent TNS surgery by a dedicated neurosurgical team (2000-2008) and 126 patients (group B) operated on by surgeons not specialized in pituitary surgery (1979-1999) were retrospectively analyzed. No significant differences were observed between the two groups in terms of delay of diagnosis, mean basal GH levels and GH nadir values, prevalence of hypopituitarism and hypertension. IGF-I SDS were significantly higher, while prevalence of IGT/diabetes was significantly lower in group B than in group A. Overall remission rate after surgery was 58.5% for group A (75% in microadenomas and 48% in macroadenomas, P=NS) and 37% for group B (P<0.05 vs group A; for microadenomas, 34% vs 75% of group A, P<0.05, for macroadenomas, 36% vs 48% of group A, P=NS). The mean delay of diagnosis was 4.9 and 5.9 years in group A and B, respectively. Our data confirm that a dedicated neurosurgical team is needed in order to improve remission rates in acromegalic patients. No changes in biochemical, clinical and neuroradiological presentation of disease were observed over the last three decades. As the high prevalence of macroadenomas negatively influences surgical cure, earlier diagnosis should be considered as mandatory to achieve a better outcome.
The Journal of Clinical Endocrinology & Metabolism, 2014
Our objective was to describe the effects of surgery and radiotherapy on hormonal control and tum... more Our objective was to describe the effects of surgery and radiotherapy on hormonal control and tumor mass in short- and long-term follow-up of TSH-secreting pituitary adenomas (TSHomas). This was a retrospective multicenter study. We collected data of 70 TSHomas (70% macroadenomas). The mean follow-up was 64.4 (range 3-324) months. Overall, 97% of patients were treated with surgery; in 27% of them radiotherapy was associated. After surgery, 75% of patients normalized thyroid function, 58% normalized both pituitary imaging and hormonal profile, 9% developed pituitary deficiencies, and 3% had tumor or hormonal recurrence, all within the first 2 years after surgery. Presurgical medical treatment did not significantly improve surgical outcome (63% vs 57%). Radiotherapy controlled hypersecretion in 37% of patients within 2 years, whereas 32% of patients developed new pituitary deficiencies from 18 to 96 months from treatment. At last follow-up, 80% of patients normalized thyroid function, whereas 20% were currently on medical treatment: 85% with somatostatin analog (SSA) alone and 15% with SSA combined with methimazole. Subjects who achieved disease control had surgery as the only treatment in 80% of cases and surgery combined with irradiation in 20%. Surgery remains the first-choice treatment for TSHoma. If surgery is successful, recurrence is rare. When surgery is unsuccessful or contraindicated, SSA and radiotherapy are effective in controlling hyperthyroidism and tumor growth in the majority of patients. The effects of radiotherapy on TSH secretion and tumor mass are greater within the first years after treatment, whereas pituitary deficiencies may occur several years later.
The Journal of Clinical Endocrinology & Metabolism, 2010
AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial is... more AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. This study was an international, multicenter, retrospective case collection/database analysis. The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P…
The Journal of Clinical Endocrinology & Metabolism, 2012
Effects of GH replacement in patients with GH deficiency (GHD) after a cure for acromegaly so far... more Effects of GH replacement in patients with GH deficiency (GHD) after a cure for acromegaly so far have been poorly studied, although its prevalence among acromegalic patients may reach the 60%. The aim of the study was to evaluate whether metabolic parameters and quality of life are improved by GH replacement in patients with prior acromegaly and severe GHD. This was a prospective study on 42 GHD subjects [22 men, mean age (sd): 48 ± 10]: 10 acromegalics treated with recombinant human GH (group A), 12 acromegalics who refused treatment (group B), and 20 subjects operated for nonfunctioning pituitary adenoma on recombinant human GH (group C). Serum IGF-I levels, lipid profile, glucose levels (fasting and after an oral glucose tolerance test), glycosylated hemoglobin, insulin resistance (homeostasis model assessment insulin resistance index), anthropometric parameters (body mass index, waist circumference, body composition), and quality of life (Questions on Life Satisfaction-Hypopituitarism Z-scores) were evaluated at baseline and after 12 and 36 months. At baseline, group B showed higher IGF sd score than group A and C, as well as better quality of life and higher post-oral glucose tolerance test glucose levels than group A. After 12-months, similarly in group A and C, the IGF-I sd score significantly increased, and body composition and lipid profile improved, without deterioration of glucose tolerance. Quality of life significantly improved too, and the baseline difference between group A and B disappeared. Results were confirmed after 36 months. In GHD acromegalic patients, GH therapy improved body composition, lipid profile, and quality of life as in patients with GHD due to nonfunctioning pituitary adenoma, without negative effects on glucose metabolism. GH replacement therapy should be considered in these patients, as in patients with GHD from other causes.
A 3.4-year-old girl was admitted to the Pediatric Department because of tall stature (116.0 cm, +... more A 3.4-year-old girl was admitted to the Pediatric Department because of tall stature (116.0 cm, +5.1 SDS) and increased height velocity (16.3 cm/year, +6.1 SDS). Basal hormonal evaluation revealed elevated insulin-like growth factor I (IGF-I) levels (938 ng/ml, nv 40-190), prolactin (PRL) (98.0 ng/ml, nv 1.7-24.0) and mean growth hormone (GH) nocturnal concentration (147 ng/ml). Basal adrenal, gonadal and thyroid functions were normal. Hand-wrist bone age was 3.6 years. Magnetic resonance imaging revealed a macroadenoma with moderate suprasellar invasion. The adenoma was surgically removed and histological characterization confirmed the diagnosis of GH/PRL-secreting adenoma. The patient was admitted to our Endocrine Unit when 7.9 years old, because of the persistence of elevated GH, IGF-I and PRL levels, although there was a slight height velocity reduction and absence of tumor recurrence. Treatment with cabergoline was initiated, but only PRL levels normalized. Afterwards, octreotide long-acting release (LAR) was added without reaching the normalization of GH and IGF-I levels. Thus, treatment with octreotide LAR was discontinued and pegvisomant was added to cabergoline, leading to the normalization of IGF-I levels and height velocity without side effects. Other anterior pituitary functions were always normal. To conclude, treatment of pituitary gigantism with pegvisomant was effective and well tolerated in a young giant unresponsive to combined cabergoline and octreotide treatment.
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Jan 13, 2016
The cyclic adenosine monophosphate (cAMP) intracellular signaling pathway mediates the physiologi... more The cyclic adenosine monophosphate (cAMP) intracellular signaling pathway mediates the physiological effects of several hormones and neurotransmitters, acting by the activation of G-protein coupled receptors (GPCRs) and several downstream intracellular effectors, including the heterotrimeric stimulatory G-protein (Gs), the cAMP-dependent protein kinase A (PKA) and cAMP-specific phosphodiesterases (PDEs). Defective G protein-mediated signaling has been associated to an increasing number of disorders, including Albright hereditary osteodistrophy (AHO) and pseudohypoparathyroidism (PHP), a heterogeneous group of rare genetic metabolic disorders due to molecular defects at the GNAS locus. Moreover, mutations in PRKAR1A and PDE4D genes have been recently detected in patients with acrodysostosis (ACRDYS), showing a skeletal and endocrinological phenotype partially overlapping with AHO/PHP. Despite the high detection rate of molecular defects by currently available molecular approaches, ab...
Most of the clinical data on the safety profile of desmopressin (DDAVP), which is an effective tr... more Most of the clinical data on the safety profile of desmopressin (DDAVP), which is an effective treatment for both polyuric conditions and bleeding disorders, originate from studies on the tailoring of drug treatment, whereas few reports exist describing severe side effects secondary to drug-drug interaction. We herein describe a case of severe hyponatremia complicated by seizure and coma due to the intake of non-steroidal anti-inflammatory drugs (NSAIDs) in a patient on DDAVP replacement therapy for central diabetes insipidus (DI). A 50-yr-old Caucasian man, with congenital central DI, developed an episode of generalized tonic-clonic seizure, resulting in coma immediately after being admitted to the Emergency Unit for weakness and emesis. Based on his medical history and clinical findings, water intoxication secondary to ketoprofen intake (200 mg/day for the last 3 days) concomitant with DDAVP replacement therapy (Minirin(®) 60 mcg 4 tablets a day) was hypothesized as being the caus...
X-linked acro-gigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplicat... more X-linked acro-gigantism (X-LAG) is a new syndrome of pituitary gigantism, caused by microduplications on chromosome Xq26.3, encompassing the gene GPR101, which is highly upregulated in pituitary tumors. We conducted this study to explore the clinical, radiological and hormonal phenotype and responses to therapy in patients with X-LAG syndrome. The study included 18 patients (13 sporadic) with X-LAG and a microduplication in chromosome Xq26.3. All sporadic cases had unique duplications and the inheritance pattern in 2 families was dominant with all Xq26.3 duplication carriers being affected. Patients began to grow rapidly as early as 2-3 months of age (median 12 months). At diagnosis (median delay 27 months), patients had a median height and weight SDS score of >+3.9 SDS. Apart from the increased overall body size, the children had acromegalic symptoms including acral enlargement and facial coarsening. More than a third of cases had increased appetite. Patients had marked hypersec...
Acromegaly guidelines updated in 2010 revisited criteria of disease control: if applied, it is li... more Acromegaly guidelines updated in 2010 revisited criteria of disease control: if applied, it is likely that a percentage of patients previously considered as cured might present postglucose GH nadir levels not adequately suppressed, with potential implications on management. This study explored GH secretion, as well as hormonal, clinical, neuroradiological, metabolic, and comorbid profile in a cohort of 40 acromegalic patients considered cured on the basis of the previous guidelines after a mean follow-up period of 17.2 years from remission, in order to assess the impact of the current criteria. At the last follow-up visit, in the presence of normal IGF-I concentrations, postglucose GH nadir was over 0.4 μg/L in 11 patients (Group A) and below 0.4 μg/L in 29 patients (Group B); moreover, Group A showed higher basal GH levels than Group B, whereas a significant decline of both GH and postglucose GH nadir levels during the follow-up was observed in Group B only. No differences in other evaluated parameters were found. These results seem to suggest that acromegalic patients considered cured on the basis of previous guidelines do not need a more intensive monitoring than patients who met the current criteria of disease control, supporting instead that the cut-off of 0.4 mcg/L might be too low for the currently used GH assay.
The diagnosis of hypothalamic-pituitary-adrenal insufficiency (HPAI) is a major clinical challeng... more The diagnosis of hypothalamic-pituitary-adrenal insufficiency (HPAI) is a major clinical challenge. The gold standard procedure remains insulin tolerance test (ITT). This study aimed to evaluate the usefulness of standard-dose corticotrophin stimulation test (SDCT) in diagnosing HPAI. In this prospective study we performed SDCT and ITT in 55 consecutive patients (37F/18M) affected by pituitary disorders. A normal response to ITT was found in 44 patients, while HPAI was diagnosed in 11. Using ITT as reference test, the ROC curve showed that a cortisol value of 18 µg/dl (500 nmol/L) at 30 min or 21.8 µg/dl (600 nmol/L) at 60 min after SDCT represents the best compromise between sensitivity and specificity in diagnosing HPAI. Moreover, 30 min cortisol values >20.3 µg/dl (560 nmol/L) or 60 min cortisol values >24.1 µg/dl (665 nmol/L) exclude HPAI. Four out of 15 patients of Group A, previously non-respondent to SDCT, showed a normal response to a second SDCT. SDCT is not a reliable tool to identify HPAI, but it appears to be more useful in confirming the normality of HPA function. When SDCT fails to exclude HPAI, ITT should be performed. If ITT is contraindicated, retesting patients by SDCT is useful before starting an unnecessary replacement therapy.
A highly polymorphic Cytosine-Adenosine (CA) repeat sequence microsatellite has been identified i... more A highly polymorphic Cytosine-Adenosine (CA) repeat sequence microsatellite has been identified in the promoter region of IGF1 gene. Several studies investigated the relationship between IGF1-(CA)n polymorphism and IGF1 levels, with conflicting results. Aim of this study was to investigate the influence of this polymorphism on clinical and biochemical characteristics of acromegalic patients. Eighty-eight acromegalic patients and 104 normal subjects were included in the study. Blood DNA was extracted and analysed by microsatellite technique using capillary electrophoresis. Patients and controls were subdivided in 19/19 [homozygous for the (CA)19 allele], 19/X [heterozygous for the (CA)19 allele] and X/X (any other genotype). The genotype frequency was significantly different between patients and controls, the proportion of 19/19 being lower (28·4% vs. 50·0%) and 19/X and X/X higher in acromegalic patients than in controls (P = 0·004). There were no significant differences in age, gender, basal and nadir GH, IGF1-SDS, tumour size, metabolic parameters, outcome and treatment among the three groups. The different frequency of genotypes in acromegalic patients vs. controls, as well as the lack of relationship between IGF1-(CA)n polymorphism and clinical and biochemical data in acromegalic patients, was confirmed using an additional alternative genotyping considering (CA)19 and (CA)20 homozygotes and heterozygotes vs. alleles with more than 19 of 20 repeats or less. Our results do not support the hypothesis that IGF-(CA)n alleles may have a significant role in determining clinical, biochemical and outcome of patients with acromegaly. The possible role of IGF1 polymorphism on susceptibility to acromegaly remains to be investigated.
ABSTRACT Transsphenoidal (TNS) surgery remains the primary therapeutic option for GH-secreting pi... more ABSTRACT Transsphenoidal (TNS) surgery remains the primary therapeutic option for GH-secreting pituitary adenomas. The aims of this study were to verify the impact of TNS surgery on treatment of acromegaly before and after identification by a dedicated neurosurgical team and to enumerate diagnostic features of the disease described over three decades. 41 patients (group A) who underwent TNS surgery by a dedicated neurosurgical team (2000-2008) and 126 patients (group B) operated on by surgeons not specialized in pituitary surgery (1979-1999) were retrospectively analyzed. No significant differences were observed between the two groups in terms of delay of diagnosis, mean basal GH levels and GH nadir values, prevalence of hypopituitarism and hypertension. IGF-I SDS were significantly higher, while prevalence of IGT/diabetes was significantly lower in group B than in group A. Overall remission rate after surgery was 58.5% for group A (75% in microadenomas and 48% in macroadenomas, P=NS) and 37% for group B (P<0.05 vs group A; for microadenomas, 34% vs 75% of group A, P<0.05, for macroadenomas, 36% vs 48% of group A, P=NS). The mean delay of diagnosis was 4.9 and 5.9 years in group A and B, respectively. Our data confirm that a dedicated neurosurgical team is needed in order to improve remission rates in acromegalic patients. No changes in biochemical, clinical and neuroradiological presentation of disease were observed over the last three decades. As the high prevalence of macroadenomas negatively influences surgical cure, earlier diagnosis should be considered as mandatory to achieve a better outcome.
The Journal of Clinical Endocrinology & Metabolism, 2014
Our objective was to describe the effects of surgery and radiotherapy on hormonal control and tum... more Our objective was to describe the effects of surgery and radiotherapy on hormonal control and tumor mass in short- and long-term follow-up of TSH-secreting pituitary adenomas (TSHomas). This was a retrospective multicenter study. We collected data of 70 TSHomas (70% macroadenomas). The mean follow-up was 64.4 (range 3-324) months. Overall, 97% of patients were treated with surgery; in 27% of them radiotherapy was associated. After surgery, 75% of patients normalized thyroid function, 58% normalized both pituitary imaging and hormonal profile, 9% developed pituitary deficiencies, and 3% had tumor or hormonal recurrence, all within the first 2 years after surgery. Presurgical medical treatment did not significantly improve surgical outcome (63% vs 57%). Radiotherapy controlled hypersecretion in 37% of patients within 2 years, whereas 32% of patients developed new pituitary deficiencies from 18 to 96 months from treatment. At last follow-up, 80% of patients normalized thyroid function, whereas 20% were currently on medical treatment: 85% with somatostatin analog (SSA) alone and 15% with SSA combined with methimazole. Subjects who achieved disease control had surgery as the only treatment in 80% of cases and surgery combined with irradiation in 20%. Surgery remains the first-choice treatment for TSHoma. If surgery is successful, recurrence is rare. When surgery is unsuccessful or contraindicated, SSA and radiotherapy are effective in controlling hyperthyroidism and tumor growth in the majority of patients. The effects of radiotherapy on TSH secretion and tumor mass are greater within the first years after treatment, whereas pituitary deficiencies may occur several years later.
The Journal of Clinical Endocrinology & Metabolism, 2010
AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial is... more AIP mutations (AIPmut) give rise to a pituitary adenoma predisposition that occurs in familial isolated pituitary adenomas and less often in sporadic cases. The clinical and therapeutic features of AIPmut-associated pituitary adenomas have not been studied comprehensively. The objective of the study was to assess clinical/therapeutic characteristics of AIPmut pituitary adenomas. This study was an international, multicenter, retrospective case collection/database analysis. The study was conducted at 36 tertiary referral endocrine and clinical genetics departments. Patients included 96 patients with germline AIPmut and pituitary adenomas and 232 matched AIPmut-negative acromegaly controls. The AIPmut population was predominantly young and male (63.5%); first symptoms occurred as children/adolescents in 50%. At diagnosis, most tumors were macroadenomas (93.3%); extension and invasion was common. Somatotropinomas comprised 78.1% of the cohort; there were also prolactinomas (n = 13), nonsecreting adenomas (n = 7), and a TSH-secreting adenoma. AIPmut somatotropinomas were larger (P = 0.00026), with higher GH levels (P = 0.00068), more frequent extension (P = 0.018) and prolactin cosecretion (P = 0.00023), and occurred 2 decades before controls (P < 0.000001). Gigantism was more common in the AIPmut group (P < 0.000001). AIPmut somatotropinoma patients underwent more surgical interventions (P = 0.00069) and had lower decreases in GH (P = 0.00037) and IGF-I (P = 0.028) and less tumor shrinkage with somatostatin analogs (P…
The Journal of Clinical Endocrinology & Metabolism, 2012
Effects of GH replacement in patients with GH deficiency (GHD) after a cure for acromegaly so far... more Effects of GH replacement in patients with GH deficiency (GHD) after a cure for acromegaly so far have been poorly studied, although its prevalence among acromegalic patients may reach the 60%. The aim of the study was to evaluate whether metabolic parameters and quality of life are improved by GH replacement in patients with prior acromegaly and severe GHD. This was a prospective study on 42 GHD subjects [22 men, mean age (sd): 48 ± 10]: 10 acromegalics treated with recombinant human GH (group A), 12 acromegalics who refused treatment (group B), and 20 subjects operated for nonfunctioning pituitary adenoma on recombinant human GH (group C). Serum IGF-I levels, lipid profile, glucose levels (fasting and after an oral glucose tolerance test), glycosylated hemoglobin, insulin resistance (homeostasis model assessment insulin resistance index), anthropometric parameters (body mass index, waist circumference, body composition), and quality of life (Questions on Life Satisfaction-Hypopituitarism Z-scores) were evaluated at baseline and after 12 and 36 months. At baseline, group B showed higher IGF sd score than group A and C, as well as better quality of life and higher post-oral glucose tolerance test glucose levels than group A. After 12-months, similarly in group A and C, the IGF-I sd score significantly increased, and body composition and lipid profile improved, without deterioration of glucose tolerance. Quality of life significantly improved too, and the baseline difference between group A and B disappeared. Results were confirmed after 36 months. In GHD acromegalic patients, GH therapy improved body composition, lipid profile, and quality of life as in patients with GHD due to nonfunctioning pituitary adenoma, without negative effects on glucose metabolism. GH replacement therapy should be considered in these patients, as in patients with GHD from other causes.
A 3.4-year-old girl was admitted to the Pediatric Department because of tall stature (116.0 cm, +... more A 3.4-year-old girl was admitted to the Pediatric Department because of tall stature (116.0 cm, +5.1 SDS) and increased height velocity (16.3 cm/year, +6.1 SDS). Basal hormonal evaluation revealed elevated insulin-like growth factor I (IGF-I) levels (938 ng/ml, nv 40-190), prolactin (PRL) (98.0 ng/ml, nv 1.7-24.0) and mean growth hormone (GH) nocturnal concentration (147 ng/ml). Basal adrenal, gonadal and thyroid functions were normal. Hand-wrist bone age was 3.6 years. Magnetic resonance imaging revealed a macroadenoma with moderate suprasellar invasion. The adenoma was surgically removed and histological characterization confirmed the diagnosis of GH/PRL-secreting adenoma. The patient was admitted to our Endocrine Unit when 7.9 years old, because of the persistence of elevated GH, IGF-I and PRL levels, although there was a slight height velocity reduction and absence of tumor recurrence. Treatment with cabergoline was initiated, but only PRL levels normalized. Afterwards, octreotide long-acting release (LAR) was added without reaching the normalization of GH and IGF-I levels. Thus, treatment with octreotide LAR was discontinued and pegvisomant was added to cabergoline, leading to the normalization of IGF-I levels and height velocity without side effects. Other anterior pituitary functions were always normal. To conclude, treatment of pituitary gigantism with pegvisomant was effective and well tolerated in a young giant unresponsive to combined cabergoline and octreotide treatment.
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