Eriselda Profka

Thyrotropin-secreting pituitary adenomas: Outcome of pituitary surgery and irradiation

OBJECTIVE 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). METHODS This was a retrospective multicenter study. RESULTS 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%. CONCLUSIONS 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.

Influence of the d3GH receptor polymorphism on the metabolic and biochemical phenotype of GH-deficient adults at baseline and during short- and long-term recombinant human GH replacement therapy

OBJECTIVE A common polymorphic variant of GH receptor (exon 3 deletion, d3GHR) has been linked with increased response to recombinant human GH (rhGH) in some patients with or without GH deficiency (GHD). The aim of the study was to investigate the impact of the GHR genotype on the phenotype of GHD adults and on the metabolic effect of rhGH therapy. DESIGN Prospective study of GHD patients evaluated before and during short- (1 year, n=100) and long-term (5 years, n=50) rhGH therapy. METHODS Effects of rhGH on IGF1 levels, body composition (body fat percentage, BF%), body mass index, lipid profile, and glucose homeostasis (fasting insulin and glucose, insulin sensitivity indexes) were evaluated according to the presence or the absence of the d3GHR variant. RESULTS The different genotype did not influence basal phenotype of GHD. Short-term rhGH determined normalization of IGF1 levels, decrease in BF%, and worsening of insulin sensitivity, independently from the presence of the d3GHR allele. A significant increase in high-density lipoprotein cholesterol occurred in the d3GHR group. Normalization of IGF1 levels and decrease in BF% were maintained after 5 years. Insulin sensitivity restored to basal values, though in d3GHR patients fasting glucose remained significantly higher than at baseline. After both 1 and 5 years, percentage of subjects with impaired glucose tolerance, similar in the two groups at baseline, decreased in fl/fl while doubled in d3GHR patients. In this last group, a long-term significant reduction in total and low-density lipoprotein cholesterol was also observed. CONCLUSION The functional difference of d3GHR may influence some metabolic effects of rhGH on GHD adults.

GH Replacement Improves Quality of Life and Metabolic Parameters in Cured Acromegalic Patients with Growth Hormone Deficiency

OBJECTIVE 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. DESIGN AND METHODS 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. RESULTS 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. CONCLUSIONS 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.

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 ± 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.

Is the 250 μg ACTH test a useful tool for the diagnosis of central hypoadrenalism in adult patients with pituitary disorders

OBJECTIVEThe 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.DESIGNIn this prospective study we performed SDCT and ITT in 55 consecutive patients (37F/18M) affected by pituitary disorders.RESULTSA 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.CONCLUSIONSSDCT 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.

Impact of IGF(CA)19 gene polymorphism on the metabolic response to GH therapy in adult GH-deficient patients

OBJECTIVE A polymorphism in the promoter region of the IGF1 gene has been linked to serum IGF1 levels, risk of diabetes, and cardiovascular diseases with conflicting results. The aim of this study was to investigate the impact of this polymorphism on the short-term (1 year, n=98) and long-term (5 years, n=50) metabolic response to recombinant human GH (rhGH) in GH-deficient (GHD) adults. DESIGN AND METHODS Prospective study on GHD adults. Different genotypes were studied by microsatellite method. According to the most frequent 192 bp allele (19 cytosine-adenosine-repeats), subjects were divided into homozygous (19/19), heterozygous (19/X), and noncarriers (X/X). RESULTS Basal characteristics of patients as well as their response to rhGH in terms of decrease in body fat percentage and increase in IGF1 levels were not different in the three genotype-groups. Conversely, after 1-year rhGH, a significant worsening of insulin sensitivity (i.e. increase in fasting glucose levels and homeostasis model assessment of insulin resistance) and a significant improvement in lipid profile (i.e. reduction in total cholesterol and LDL-cholesterol) were recorded only in homozygous subjects. In the long-term, insulin sensitivity was restored in all the patients, while a significant improvement in lipid profile was observed in homozygous and heterozygous subjects, but not in noncarrier subjects. No difference in rhGH dose among groups was recorded throughout the study. CONCLUSIONS In GHD adults, the presence of the WT allele in the IGF1 gene promoter may enhance sensitivity to either negative or positive metabolic changes induced by rhGH.

Focus on GH deficiency and thyroid function

The relationships between GH system and hypothalamic-pituitary-thyroid axis are complex and not yet fully understood. The reported effects of GH administration on thyroid status of GHD patients have been remarkably divergent. This review will focus on the main studies aimed to clarify the effects of GH on thyroid function, firstly going through the diagnosis of central hypothyroidism and its possible pitfalls, then elucidating the possible contexts in which GHD may develop and examining the proposed mechanisms at the basis of interactions between the GH-IGF-I system and the hypothalamic-pituitary-thyroid axis.

Contents Vol. 102, 2015

77 Abstracts of the 12th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease March 11–13, 2015, Barcelona, Spain Guest Editors: Reed, N. (Glasgow); Couvelard, A. (Paris); Ruszniewski, P. (Clichy) 169 ENETS Newsletter Summer 2015 E-Mail karger@karger.com www.karger.com