Agostino Paoletta

Persistent Psychological Distress in Patients Treated for Endocrine Disease

Background: The purpose of the study was to assess the frequency and characteristics of psychological distress, even after adequate treatment, in the heterogeneous population of an endocrine outpatient clinic. Methods: 146 endocrine patients (31 males/115 females; age 39.4 ± 12.5 years), who were cured or in remission, were studied in a university endocrine outpatient clinic. Semistructured clinical interviews to assess psychiatric (Structured Clinical Interview for DSM-IV) and psychological (Diagnostic Criteria for Psychosomatic Research, DCPR) diagnoses were employed and were supplemented by self-rated instruments (the Psychosocial Index and the Medical Outcome Study short form General Health Survey) which could provide the patients’ perception of their own quality of life. Results: There were 118 patients (81%) who presented with at least 1 psychiatric (DSM-IV) or psychological (DCPR) diagnosis. The most frequent diagnostic findings were generalized anxiety disorder (29%), major depression (26%), irritable mood (46%), demoralization (34%) and persistent somatization (21%). By self-rated instruments, patients with at least 1 DSM-IV or DCPR diagnosis reported significantly more stressful life circumstances, psychological distress and an impaired quality of life compared to those who had none. Conclusions: A high prevalence of psychological distress may be encountered in the long-term follow-up of endocrine patients. A biopsychosocial consideration of the person and his/her quality of life appears to be mandatory for improving therapeutic effectiveness in endocrine disorders.

Effect of Surgical Treatment on Hypertension in Cushing’s Syndrome

The effect of a surgical cure of hypercortisolism on hypertension in 54 patients with Cushings syndrome was assessed. The correlation between preoperative duration of hypertension and posttreatment blood pressure was significant (P < .01). Restoration of normal cortisol was associated with blood pressure normalization in 39 out of 54 cases. Duration of hypertension of patients with normalized blood pressure was significantly shorter than that of patients with persistent hypertension postoperatively (P < .0001). Duration of hypertension, ie, long-lasting exposure to increased cortisol, appears to be the determinant of persistent hypertension following successful surgery in Cushings syndrome.

Response of hypertension to conventional antihypertensive treatment and/or steroidogenesis inhibitors in Cushing's syndrome

Abstract. Objectives. To evaluate the effect of conventional antihypertensive drugs and/or inhibitors of steroid production in the management of hypertension in Cushings syndrome.

Psychosocial impairment in patients treated for pituitary disease: a controlled study

Objective  To verify whether patients with pituitary disorders in remission and on appropriate treatment display significant differences in psychological distress compared to healthy controls and other patients treated for nonpituitary endocrine disorders.

Slow-Release Lanreotide Treatment in Acromegaly: Effects on Quality of Life

Background: It is not known whether medical treatment to lower growth hormone (GH) and insulin-like growth factor (IGF)-1 levels may improve the compromised quality of life of patients with acromegaly. Methods: We studied the effects on quality of life of the slow-release somatostatin analogue lanreotide, 30 mg i.m., every 14 days for 2 months in 10 patients with active acromegaly (8 females/2 males, mean age 57.3 ± 11.4). Hormone measurements and psychometric evaluation by means of self-rating scales were carried out in baseline conditions and after 1 and 2 months. The Symptom Questionnaire (SQ), the Cognitive Scale of the Screening List for Psychosocial Problems by Kellner and the Social Situation Questionnaire by Marks were employed. Results: Together with a significant decrease in GH and IGF-1, treatment with lanreotide significantly improved SQ psychological distress, SQ well-being and Social Situation Questionnaire social fears. Conclusion: Medical treatment with lanreotide may improve the quality of life of patients with acromegaly. Being an open trial, changes could be due to nonspecific effects. However, they did not fade at 2 months. Improvement involved fears of social situations that have been linked to GH abnormalities.

Selective venous sampling in the differential diagnosis of ACTH-dependent Cushing's syndrome

Bilateral simultaneous inferior petrosal sinus sampling, associated with the oCRH stimulation test (100 micrograms i.v. as a bolus) was performed in 22 patients with Cushings syndrome and no signs of pituitary abnormalities. Catheters were inserted into both femoral veins. More than one site in the superior and inferior vena cava was sampled before reaching the inferior petrosal sinuses. Blood samples for ACTH and beta-endorphin were gently aspirated from both petrosal sinuses and from a peripheral vein simultaneously. Blood was drawn at 0, 5, 10 and 15 min after oCRH injection. Seventeen of 22 patients showed an ipsilateral to peripheral vein ratio higher than 1.5, and 12 patients showed a lateralization of ACTH levels after oCRH stimulation. Seventeen patients underwent transsphenoidal pituitary surgery. Nine patients had a pituitary adenoma at the expected side; 1 at the contralateral side, while in 2 it was central. Three of 4 patients in whom the ipsilateral/peripheral ratio was less than 1.5 had the highest ACTH levels at the superior or inferior vena cava, not responsive to oCRH stimulation. One of these had a mediastinal and one a pulmonary mass. The third one, with an occult ectopic source, is still under investigation. At immunohistochemical and biological in vitro studies, both tumors were shown to secrete ACTH. In 13 patients in whom both beta-endorphin and ACTH measurements were performed, these hormones showed similar patterns of response. In conclusion, simultaneous bilateral petrosal sinus catheterization is a useful tool in the differential diagnosis of Cushings syndrome as concerning pituitary and ectopic forms.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Arterial Stiffness Indexes in Acromegaly

OBJECTIVE Acromegaly is associated with increased cardiovascular morbidity and mortality and with specific heart and vascular abnormalities. The aim of our study was to investigate arterial stiffness using the ambulatory arterial stiffness index (AASI) and symmetric AASI (Sym-AASI), two indexes derived from 24-h ambulatory blood pressure monitoring (ABPM), in a group of normotensive and hypertensive patients with active acromegaly, compared with normotensive controls (NOR-CTR) or hypertensive controls (HYP-CTR). SUBJECTS AND METHODS Ninety-six consecutive patients with active acromegaly (46 males, mean age 49±14 years) underwent 24-h ABPM and evaluation of cardiovascular risk factors. Based on ABPM measurement, acromegalic patients were divided into 64 normotensive (normotensive acromegalic patients (NOR-ACRO)) and 32 hypertensive (hypertensive acromegalic patients (HYP-ACRO)) patients, and were compared with 35 normotensive (NOR-CTR) and 34 hypertensive (HYP-CTR) age-, sex,- and ABPM-matched control subjects. RESULTS The AASI and Sym-AASI indexes were significantly higher in acromegalic patients than in controls, either in the normotensive (NOR-ACRO vs NOR-CTR, P<0.0001 for AASI and P=0.005 for Sym-AASI) or in the hypertensive (HYP-ACRO vs HYP-CTR, P=0.01 for AASI and P=0.01 for Sym-AASI) group. Multiple logistic regression analysis showed a significant association of the highest AASI tertile with serum IGF1 (P=0.034) in the whole acromegalic group. CONCLUSION AASIs are increased in acromegaly, independent of blood pressure (BP) elevation, and may have an important role in predicting cardiovascular risk in this disease.

Inhibition of Pituitary β-Endorphin by ACTH and Glucocorticoids

β-Endorphin and ACTH are secreted concomitantly in baseline conditions and in response to physiological and pharmacological stimuli. However, few and contradictory data are available on their feedback

Patterns of ACTH Response to oCRH in Cushing’s Disease: Correlation with Histological/Immunocytochemical Findings

The most common lesion in Cushings disease is an anterior pituitary adenoma. However, normal or hyperplastic corticotropic pituitary tissue has also been found in some cases. In an attempt to distinguish the patterns of ACTH response to oCRH in different forms of anterior pituitary hypersecretion, 17 patients with pituitary adenoma and 17 without pathological evidence of adenoma were studied. These patients underwent transsphenoidal pituitary surgery by the same surgeon and were retrospectively evaluated. The diagnosis of pituitary lesions was confirmed by microscopical and immunohistochemical studies. Patients without pituitary adenoma showed a higher and more prolonged mean plasma ACTH response than that observed in patients with pituitary tumors. In patients with pituitary adenoma, the peak ACTH response was observed within 30 min after oCRH administration, and was followed by a gradual decrease to basal levels in the following 30 min. In those cases in whom no pituitary adenoma was found, oCRH injection produced a marked increase in plasma ACTH levels during the first 60 min with a slower decline at the subsequent time points. The mean response curves of the two groups, analyzed by Beherens-Fischer nonparametric ANOVA, showed significant differences, either when they were compared globally (p < 0.01), or at single time points. Differences in ACTH response to oCRH stimulation support the hypothesis of different pathogenetic mechanisms leading to ACTH hypersecretion in Cushings disease with and without pituitary adenoma.

A case of nephrotic syndrome hidden by Cushing's disease.

The literature reports steroid-responsive diseases co-existing with Cushing’s syndrome, which fully develop after remission of endogenous hypercortisolism. They mainly include autoimmune or allergic diseases [1]. We describe a case of nephrotic syndrome, diagnosed during work-up for Cushing’s disease, and subsequently unmasked by successful trans-sphenoidal hypophysectomy. A 21-year-old female presented a recent occurrence of weight gain, acne, hirsutism, and muscle weakness. Physical examination revealed truncal obesity, moon face, buffalo hump, and a mild bilateral ankle oedema; blood pressure was 120/80 mmHg. No signs (i.e., skin rashes, arthritis, and peripheral neuropathy) or symptoms (i.e., pain, heat, and swelling) of systemic inflammatory disease were present, and past history was negative. She was investigated for hypercortisolism. 24-hour urinary free cortisol was high at 385 lg/24 h (normal range 30–250 lg/ 24 h), and 1-mg overnight dexamethasone test failed to suppress plasma cortisol (42 lg/dl). Plasma ACTH was high on two consecutive days (69.5 and 62.3 pg/ml, normal range 10–45 pg/ml), supporting the diagnosis of ACTHdependent Cushing’s syndrome. Brain MRI revealed a 5-mm-diameter tumor mass in the pituitary gland (Fig. 1a, b), and trans-sphenoidal pituitary surgery was scheduled. During pre-surgery hospitalization, routine biochemical tests revealed hypoalbuminemia (20 g/l), hypercholesterolemia (345 mg/dl), and proteinuria (3.2 g/day) in the presence of normal serum creatinine levels (1.0 mg/dl). A surgical resection of pituitary microadenoma was performed, and immunocytochemistry showed selective ACTH immunostaining. After surgery, the patient was immediately treated with steroid replacement therapy (cortisone acetate 25 ? 12.5 mg/day) to prevent adrenal insufficiency. Two months later, steroid coverage was reduced. Shortly after steroid withdrawal, ACTH and urinary cortisol normalized, and marked improvement in clinical features of hypercortisolism was observed. However, the patient continued to complain of muscle weakness and to have clinical evidence of peripheral edema; blood pressure tended to be high (150/95 mmHg). Biochemical re-assessment revealed persistence of low serum albumin (22 g/l), hypercholesterolemia (380 mg/dl), and worsening of proteinuria (6.9 g/24 h); renal function was still normal. She was admitted to Hospital for further investigation. A renal biopsy was performed. Light microscopic examination showed a marked mesangial expansion due to matrix enlargement with a mild degree of endocapillary cellular proliferation (Fig. 1c), a pattern consistent with a membranous glomerular disease [2]. Common secondary causes of nephrotic syndrome, i.e., diabetes mellitus, systemic lupus erythematosus, hepatitis, HIV infection, or amyloidosis, were excluded, leading to a diagnosis of a primary form of glomerulonephritis. A combination of loop diuretics, angiotensin-converting enzyme inhibitors, and corticosteroids was initiated. The three-month pharmacological A. Paoletta Endocrinology Outpatient Service, Cittadella Hospital, Cittadella, Italy