Giovanni Amato

Long‐term effects of lanreotide SR and octreotide LAR® on tumour shrinkage and GH hypersecretion in patients with previously untreated acromegaly

background and objective The therapeutic efficacy of lanreotide SR and octreotide LAR® has been studied widely in patients treated previously with neurosurgery and/or radiotherapy. These therapies limit the evaluation of the long‐term effects of somatostatin analogues on tumour shrinkage. Neurosurgical and radiotherapy treatments cause irreversible anatomical changes in pituitary morphology, which can make accurate evaluation of tumour shrinkage difficult. The aim of this study was to investigate the therapeutic efficacy of lanreotide SR and octreotide LAR® in previously untreated patients with acromegaly. We aimed to investigate the long‐term effects of these drugs on tumour shrinkage and growth hormone (GH) hypersecretion without the confounding influences of previous therapy.

Recombinant Human TSH Modulates In Vivo C‐Telopeptides of Type‐1 Collagen and Bone Alkaline Phosphatase, but Not Osteoprotegerin Production in Postmenopausal Women Monitored for Differentiated Thyroid Carcinoma

In women monitored for thyroid carcinoma, short‐term stimulation with rhTSH induced an acute decrease in serum C‐telopeptides of type‐1 collagen and an increase in serum BALP levels without any effect on OPG production. The inhibitory effect of TSH on bone resorption occurred only in postmenopausal women who showed low BMD and a high bone turnover rate as an effect of L‐thyroxine suppressive therapy.

Longitudinal Study of Antibodies against Thyroid in Patients Undergoing Interferon-α Therapy for HCV Chronic Hepatitis

Seventy-five patients (50 M, 25 F), affected by chronic hepatitis caused by hepatitis C virus (HCV), without clinically overt thyroid disease, underwent r-interferon (IFN)-alpha-2a treatment (3-6 MU, 3 times/week) for 12 months. They were tested for thyroid function and for thyroid autoantibodies before (A), 6 (B) and 12 (C) months after the beginning of treatment and after 6 (D) months off therapy. Antithyroglobulin antibodies (Tg-Ab) and TSH were measured by IRMA, antiperoxidase antibodies (TPO-Ab), free T3 (FT3) and free T4 (FT4) by RIA, thyrotropin receptor antibodies (TR-Ab) by RRA. None of the patients showed TR-Ab positivity throughout the study. The number of the patients with one or both antithyroid antibodies progressively increased during treatment (A 10.7%; B 26.7%; C 45.3%) and decreased when off therapy (D 22.7%) with none of them positive for Tg-Ab alone (TPO-Ab 6.7%; Tg-Ab+TPO-Ab 16%). Tg-Ab increased during rIFN (median: A 29.0; B 35.0; C 73.0 U/ml) but decreased when off therapy (D 29.0 U/ml). Instead, TPO-Ab significantly increased throughout the study (A 1.0; B 3.0; C 6.0; D 7.0 U/ml). However, some patients showed for the first time an appearance of antibodies when off therapy. Five patients showed both antibodies and thyroid dysfunction: 2 at B, 2 at C, and 1 at D. Only 1 developed mild transient hyperthyroidism while the other 4 developed hypothyroidism, persistent however only in 1 case. Our study confirms that rIFN-alpha-2a frequently induces thyroid autoimmunity. TPO-Ab seems more useful than Tg-Ab in monitoring the immunological response.(ABSTRACT TRUNCATED AT 250 WORDS)

Grey-scale analysis allows a quantitative evaluation of thyroid echogenicity in the patients with Hashimoto's thyroiditis

objective In the present study we have performed a grey‐scale quantitative analysis of thyroid echogenicity in the patients affected by Hashimotos thyroiditis (HT), obtaining a numerical estimate of the degree of hypoecogenicity associated with the appearance of thyroid dysfunction.

Low dose recombinant human growth hormone normalizes bone metabolism and cortical bone density and improves trabecular bone density in growth hormone deficient adults without causing adverse effects

OBJECTIVES Prolonged GH deficiency Induces alterations In bone metabolism and structure. Trials In GH deficient adults (GHDA) employing high dose GH replacement therapy produced conflicting results, and caused several adverse effects. This prompted us to study the effects of rhGH treatment on bone metabolism and structure at lowest doses so far used.

Temporal relationship between the appearance of thyroid autoantibodies and development of destructive thyroiditis in patients undergoing treatment with two different type-1 interferons for HCV-related chronic hepatitis: A prospective study

In this prospective study we performed repeated evaluations of thyroid status in patients undergoing treatment with different preparations of recombinant interferons (IFNs), in order to identify early markers of thyroid dysfunction. Moreover, we aimed to investigate whether the development of thyroid dysfunction was related to the appearance of thyroid autoimmunity. Our study included 51 consecutive patients without pre-existing thyroid disease, admitted to our hospital for Hepatitis C virus (HCV)- related chronic hepatitis. Thirty-six patients (Gr. A) were treated with IFN-α 2b plus ribavirin (RIBA), whereas 15 patients (Gr. B) underwent treatment with IFN-αcon-1 (CIFN) plus RIBA. Thyroid autoimmunity and function were prospectively evaluated before, every month during treatment and for 6 months after IFN withdrawal. At study entry, all patients were euthyroid and negative for thyroid autoantibodies. In Gr. A, 10 patients developed thyroid autoimmunity after a median period of 3 months (range: 1–6) treatment with IFN-α+RIBA. At the time of appearance of thyroid autoantibodies, 4 patients developed destructive thyrotoxicosis (overt in one case, subclinical in 3 cases), while other 4 patients showed a high reduction of serum TSH levels (median decrease: − 75.7%, range: −61.9- −84.2), which reached the low values of normal range. After a median period of 2 months (range: 1–3) from these biochemical abnormalities, 6 patients continuing antiviral treatment developed hypothyroidism (overt in 3 cases and subclinical in the other 3). In Gr. B, 5 patients developed thyroid autoimmunity after a median period of 3 months (range: 2–10) of treatment with CIFN+RIBA. Soon after the appearance of thyroid autoantibodies, all patients developed an overt thyrotoxicosis (with hyperthyroidism in 2 cases). Antiviral treatment was discontinued in all 5 cases. Thereafter, thyroid function recovered spontaneously without significant modifications of serum TGAb and TPOAb levels until the end of the study. In conclusion our prospective study demonstrated that: 1) the appearance of thyroid autoantibodies during treatment with IFN was accompanied in most cases by the occurrence of a destructive process in the thyroid gland; 2) The clinical expression of destructive thyroiditis was more evident in patients treated with CIFN than that in patients treated with IFN; 3) The thyroid clinical outcome of these patients was strictly correlated to the continuation of cytokine treatment.

Current guidelines for adult GH replacement.

Growth hormone deficiency (GHD) in adults may be of either adult or childhood onset and may occur as isolated GHD or as multiple hormone deficiencies. Adult-onset GHD usually results from damage to the pituitary gland or hypothalamus. Such damage may be caused by a tumor in the area or by treatment for a tumor (surgery or radiotherapy). Childhood–onset GHD presents with low growth velocity, is often idiopathic, and may continue in adult life in up to 50% of cases. GHD may also develop in some children and adult survivors of childhood malignancy following cranial irradiation or chemotherapy. Adult GHD commonly presents with the following problems:

Recombinant human growth hormone treatment at low doses does not significantly change thyroid function in growth hormone deficient adults.

Pituitary-thyroid changes have been reported during recombinant human growth hormone (rhGH) therapy at the dose commonly used in pre-puberty. We have previously demonstrated that low doses of rhGH were able to normalize body composition and both cardiac structure and function in growth hormone deficient adults (GHDA), without causing any of the side effects described when the GHDA were treated with doses commonly employed in the GHD children. The aim of this study was to evaluate the behaviour of pituitary-thyroid parameters in GHDA undergoing such a low dose of rhGH treatment. We studied 9 (2 females and 7 males, 25–34 yr) GHDA, 7 congenital and 2 acquired GH deficiency, before, during and after a 12-month rhGH treatment at dose of 10 μg/kg/day (=70 μg/kg/week) divided in 3 injections, administered sc at 20:00 h on Monday, Wednesday and Friday, respectively. Thyroid deficiency and other hormonal deficiencies, when present, had been adequately corrected with replacement therapy. Serum IGF1, T3, T4, free-T3, free-T4, TSH, reverse-T3, T3/T4 and FT3/FT4 ratios were studied basally, every 3 months during the 12-month rhGH treatment and every 3 months for a period of 12 months off therapy. Analysis of variance (ANOVA) was performed as statistical method. All parameters (except IGF1) did not show any variation during and after rhGH treatment at low doses. The alterations of T3 and T4 metabolism, in the sense of a T3 increase and a T4 reduction, caused sometimes by rhGH treatment, could be due to the higher doses used and therefore should be considered another side effect, like artrhalgia, fluid retention, carpal tunnel syndrome, etc.

Iodized salt improves the effectiveness of l‐thyroxine therapy after surgery for nontoxic goitre: a prospective and randomized study

objective To investigate whether the addition of iodized salt to daily diet in thyroidectomized patients for nontoxic goitre could influence the effectiveness of nonsuppressive l‐thyroxine (L‐T4) therapy on thyroid remnant size, during 12 months’ follow‐up after thyroid surgery.

Insulin-like growth factor binding protein-3 reduction in follicular fluid in spontaneous and stimulated cycles

OBJECTIVE To investigate serum and follicular fluid insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) behavior in spontaneous and in superstimulated cycles. DESIGN Estradiol, GH, IGF-I, and IGFBP-3 were evaluated in serum and in follicular fluid during spontaneous and stimulated cycles. SETTING Department of Obstetrics and Gynecology, University of Naples, Naples, Italy. PATIENT(S) Ninety-two patients with regular menstrual cycles and tubal and/or male factor infertility undergoing treatment with an IVF program. INTERVENTION(S) The superstimulated IVF program uses leuprolide acetate suppression followed by hMG in a sequential manner in the subsequent cycle. After sufficient follicular development, hCG was administered, followed 34-36 hours later by oocyte retrieval. MAIN OUTCOME MEASURE(S) Growth hormone, IGF-I, and IGFBP-3 were assayed by RIA and immunoradiometric assay techniques. RESULT(S) Growth hormone levels in serum and in follicular fluid were higher after FSH-stimulated cycles than after physiologic cycles. Serum and follicular fluid IGF-I did not change during physiologic and FSH-stimulated cycles. Serum IGFBP-3 decreased only in FSH-stimulated cycles. Levels of IGFBP-3 in follicular fluid were lower than serum levels in late follicular phase both in physiologic and in FSH-stimulated cycles. CONCLUSION(S) Reduction of IGFBP-3 is an important mechanism allowing a larger local availability of free IGFs, which modulate the response of follicles to gonadotropin stimulation. This effect is amplified in stimulated cycles.