Acromegalia

Il contribuito tratta di epidemiologia, diagnosi e terapia dell'acromegalia nel paziente anzian

Long-term basal and dynamic evaluation of hypothalamic-pituitary-adrenal (HPA) axis in acromegalic patients

Objective: Long-term effects of trans-naso-sphenoidal surgery (TNS) or long-acting somatostatin analogs (SSA) on the function of hypothalamic- pituitary-adrenal (HPA) axis have been poorly investigated. Aim of this study was to evaluate HPA axis integrity during the follow-up in patients with GH-secreting pituitary adenomas and preserved HPA function post-TNS or prior SSA. Design and patients: This retrospective study investigated 36 acromegalic patients (16M and 20F, age: 47 ± 13 years), 20 of whom cured by TNS and 16 controlled by SSA therapy (12 previously operated and 4 in primary medical therapy), before and after long-term follow-up (median: 72 months, range: 12-240). No patient previously underwent radiotherapy. Measurements: HPA function was studied by morning circulating cortisol and ACTH levels, 24-h urinary free cortisol (UFC) and cortisol response to low-dose short Synacthen test (LDSST, 1 μg) with a peak > 500 nmol/l as cut-off for normal function. Results: Serum basal cortisol, ACTH and UFC levels were in the normal range and did not significantly change over time. As far as the cortisol peak after LDSST is concerned, 12 patients (32%, 8 TNS and 4 SSA) developed biochemical hypoadrenalism. None of the patients in primary medical therapy showed cortisol peak < 500 nmol/l. No significant correlations between HPA axis deterioration and follow-up duration, serum GH/IGF-I levels, occurrence of other pituitary deficiencies, presence of secondary empty sella, changes in tumour or residual volume were observed. Conclusions: The HPA axis function must be carefully monitored over the time by dynamic testing in all acromegalic patients, independently from the type of treatment

Severe water intoxication secondary to the concomitant intake of non-steroidal anti-inflammatory drugs and desmopressin : a case report and review of the literature

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\uae 60 mcg 4 tablets a day) was hypothesized as being the cause of the severe euvolemic hypotonic hyponatremia (natremia 113 mEq/l, plasma osmolality 238 mOsm/Kg). After standard emergency procedures, appropriate gradual restoration of serum sodium levels to the normal range was achieved in 72 hours. Hydratation was maintained according to water excretion and desmopressin therapy was re-introduced. We discuss this case report in the context of the published literature. The present report first highlights the potentially life-threatening side effects associated with over-the-counter NSAIDs during DDAVP replacement therapy for central DI. Risks and benefits of co-treatment should be carefully considered and therapeutic alternatives to NSAIDs should be recommended to patients with central DI in order to improve DDAVP safet

A Case Report of Severe Hypotonic Hyponatremia Secondary to Concomitant Intake of Desmopressin Replacement Therapy and Non-Steroidal Anti-Inflammatory Drugs

Background: Desmopressin (DDAVP) is an effective treatment of both polyuric conditions and bleeding disorders. Most of the data on safety profile of desmopressin (DDAVP) derives from studies on titration of drug treatment, whereas few reports describe severe side effects secondary to drug-drug interaction.Clinical case: We report the case of a 50-yr-old Caucasian man, affected with congenital central diabetes insipidus (DI), admitted to the Emergency Unit for ingravescent nausea, emesis and weakness since twelve hours. A recent endocrinological evaluation reported a normal anterior pituitary function. Shortly after admission, he developed an episode of generalized tonic-clonic seizure, resulting in coma. The post-critic physical examination did not showed clinical signs of volume expansion or depletion. Moreover, brain CT scan was normal. Based on his medical history and clinical findings, water intoxication secondary to non steroidal anti-inflammatory drug (NSAID) intake (ketoprofen, 200 mg/day for the last 3 days for cervical pain) concomitant with DDAVP replacement therapy (Minirin\uae 60 mcg 4 tablets a day) was hypothesized as cause of the severe euvolemic hypotonic hyponatremia observed at entry (natremia 113 mEq/l, n 135-145 mEq/l; plasma osmolality 238 mOsm/Kg, n 275-295 mOsm/Kg) and the acute fall in sodium levels was considered responsible for seizures and coma. After emergency procedures, the aquaretic tolvaptan (Samsca\uae 7.5 mg) was administered and hydratation was maintained according to water excretion. At the same time, desmopressin substitution was withdrawn. The patient completely recovered in 72 hours and was discharged 10 days after with reinstatement of desmopressin replacement therapy.Conclusions: Although several cases of hyponatremia in patients on DDAVP for different indications have been reported, no study has so far highlighted the potentially life-threatening side effects associated with NSAIDs intake during DDAVP replacement therapy for central diabetes insipidus. In order to improve DDAVP safety, risks and benefits of co-treatment should be carefully considered and therapeutic alternatives to NSAIDs should be recommended to patients with central diabetes insipidus

Analysis of short- and long-term metabolic effects of growth hormone replacement therapy in adult patients with craniopharyngioma and non-functioning pituitary adenoma

Purpose: Adult patients operated for craniopharyngioma develop more frequently GH deficiency (GHD) than patients operated for non-functioning pituitary adenoma (NFPA). The aim of the study was to compare both short- (1 year) and long-term (5 years) effects of rhGH in 38 GHD adult patients (19 operated for Craniopharyngioma (CP) and 19 for NFPA). Methods: IGF-I levels, body composition (BF %), BMI, lipid profile and glucose homeostasis were evaluated in all patients. Pituitary MRI was performed at baseline and during follow-up, as needed. Results: At baseline no difference between the two groups was observed, apart from a higher prevalence of diabetes insipidus in CP patients (79 vs 21 %). After 12 months, IGF-I SDS normalized and BF % significantly decreased only in the NFPA group. During long-term treatment, decrease in BF % and improvement in lipid profile shown by reduction in total- and LDL-cholesterol were present in NFPA group only, while increase in insulin levels and HbA1c and decrease of QUICKI were observed in CP patients only. Accordingly, after long-term therapy, the prevalence of metabolic syndrome (MS) was significantly higher in CP than in NFPA group (37 % in CP and in 5 % in NFPA group; p &lt; 0.05). Conclusion: The present data suggest that CP patients are less sensitive to the positive rhGH effects on lipid profile and BF % and more prone to insulin sensitivity worsening than NFPA patients, resulting in increased prevalence of MS in CP only

Recurrence of hyperprolactinemia following dopamine agonist withdrawal and possible predictive factors of recurrence in prolactinomas

Background: The optimal duration of cabergoline (CAB) treatment of prolactinomas that minimizes recurrences is not well established. 2011 Endocrine Society Guidelines suggested that withdrawal may be safely undertaken after 2\ua0years in patients achieving normoprolactinemia and tumor reduction. Materials: We analyzed 74 patients (mean age\ua0=\ua046.9\ua0\ub1\ua014.4, M/F\ua0=\ua019/55, macro/micro\ua0=\ua018/56) bearing a prolactinoma divided in 3 groups: group A (23) treated for 3\ua0years, group B (23) for a period between 3 and 5\ua0years, and group C (28) for a period >5\ua0years. CAB therapy was interrupted according to Endocrine Society Guidelines. Prolactin (PRL) levels were measured 3, 6, 12 and 24\ua0months after withdrawal. Recurrence was defined with PRL levels 6530\ua0ng/ml. Results: Groups did not differ in pretreatment PRL levels (123.2\ua0\ub1\ua0112.1, 120.9\ua0\ub1\ua0123.8, 176.6\ua0\ub1\ua0154.0), pituitary deficit (4, 17, 17\ua0%), mean CAB weekly dose (0.7\ua0\ub1\ua00.4, 0.6\ua0\ub1\ua00.3, 0.7\ua0\ub1\ua00.4) and PRL levels before withdrawal (17.1\ua0\ub1\ua019.6, 11.4\ua0\ub1\ua08.8, 13.8\ua0\ub1\ua013.5). Recurrence occurred within 12\ua0months in 34 patients (45.9\ua0%), without significant differences among groups. Neuroradiological evaluation showed a significantly higher presence of macroadenoma in group C (13, 17 and 39\ua0%, respectively). Recurrence rate of hyperprolactinemia did not depend on sex, tumor size or CAB dose but it was significantly correlated with PRL levels at diagnosis and before withdrawal (p\ua0=\ua00.03). Finally, patients with pituitary deficit at diagnosis showed a significantly higher recurrence rate (p\ua0=\ua00.03). Conclusions: The study provides additional evidence that prolonging therapy for more than 3\ua0years does not reduce recurrence rate. In particular, recurrence risk was similar in micro- and macroadenomas, and higher in patients with pituitary deficits at diagnosis

Eight-year follow-up of a child with a GH/prolactin-secreting adenoma : efficacy of pegvisomant therapy

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. Copyrigh

Hypothalamic-Pituitary Axis in Non-Functioning Pituitary Adenomas : focus on the Prevalence of Isolated Central Hypoadrenalism

Introduction: Non-functioning pituitary adenomas (NFPA) account for about 40% of pituitary tumors. Pituitary deficiencies are present at diagnosis in 60-80% of NFPA, and, classically, growth hormone (GH) secretion is lost first, while adrenocorticotropic hormone is expected to disappear last. The aim of this study was to evaluate the incidence of multiple or isolated pituitary deficiencies in a large series of NFPA. Materials and Methods: We retrospectively analyzed data on 218 NFPA cases (59% females, 59% with macroadenomas, average age: 50.2 \ub1 17 years) followed up at our center from 1990 to 2013. At diagnosis all patients had a complete evaluation of pituitary function in basal conditions and provocative tests for the hypothalamic-pituitary-adrenal axis, while tests for GH deficiency (GHD) were carried out in 38%. Results: 52.3% of patients (65.6% of macroadenomas, 33.3% of microadenomas) presented at least 1 pituitary deficiency: isolated deficiency in 29.8%, multiple deficiencies in 30% and panhypopituitarism in 9%. Isolated deficiencies were hypogonadism in 11.5% of patients (8% in micro-, 14% in macroadenomas), hypoadrenalism in 10.1% (14% in micro-, 7% in macroadenomas) and GHD in 8.3% (8.9% in micro-, 7.8% in macroadenomas). About 30% of microadenomas had at least 1 pituitary deficiency at diagnosis, independently of tumor localization within the sellar region. Conclusions: The presence of isolated hypoadrenalism suggests that the order of appearance of hypopituitarism does not always follow the one expected. Given the relatively high prevalence of isolated hypoadrenalism even in microadenomas, we suggest a full assessment of basal and dynamic pituitary function in all NFPA regardless of tumor size