Role of a long-acting somatostatin analogue (SMS 201-995) in the treatment of acromegaly

Background: Somatotropinomas are rare in childhood and frequently associated with genetic mutations. AIP mutations are found in 20–25% cases and cause aggressive somatotropinomas, often resistant to somatostatin analogues. Aims: To assess responses to multimodal therapy including pegvisomant in 2 children with sporadic somatotropinomas due to AIP mutations. Case Description: We report 2 children, a boy aged 13 and a girl aged 10, with rapid growth, visual impairment, and growth hormone hypersecretion. Magnetic resonance imaging confirmed a pituitary macroadenoma with parasellar extension in both. Despite multiple surgical attempts to debulk tumour mass, residual tumour persisted. Genetic analysis showed two different AIP mutations (patient 1: c.562delC [p.Arg188Glyfs*8]; patient 2: c.140_ 163del24 [p.Gly47_Arg54del8]). They were initially treated with a long-acting somatostatin analogue (octreotide LAR 30 mg/month) and cabergoline as a dopamine agonist, with the later addition of pegvisomant titrated up to 20 mg/day and with radiotherapy for long-term control. Somatostatin analogue was ceased due to patient intolerance and lack of control. Patient 1 had normalization of insulin-like growth factor-1 (IGF-1) after 5 months of combined therapy with pegvisomant and cabergoline. For patient 2, normalization of IGF-1 was achieved after 2 months of cabergoline and pegvisomant. Conclusion: AIP-associated tumours can be resistant to management with somatostatin analogues. Pegvisomant can safely be used, to normalize IGF-1 levels and help control disease.

Download Full-text

The Role of a Long-Acting Somatostatin Analogue (SMS 201-995) in the Management of a Patient with a Benign Insulin-Secreting Adenoma of the Pancreas and a Postoperative Pancreatic Fistula

Scandinavian Journal of Gastroenterology ◽

10.3109/00365528609087456 ◽

1986 ◽

Vol 21 (sup119) ◽

pp. 217-222 ◽

Cited By ~ 15

Author(s):

E. Lewis ◽

S. Tsai ◽

A. Vinik

Keyword(s):

Pancreatic Fistula ◽

Postoperative Pancreatic Fistula ◽

Somatostatin Analogue ◽

Long Acting

Download Full-text

MANAGEMENT OF ENDOCRINE DISEASE: GH excess: diagnosis and medical therapy

Acta Endocrinologica ◽

10.1530/eje-13-0532 ◽

2014 ◽

Vol 170 (1) ◽

pp. R31-R41 ◽

Cited By ~ 14

Author(s):

Marianne Andersen

Keyword(s):

Polyclonal Antibodies ◽

Somatostatin Analogues ◽

Somatostatin Analogue ◽

Primary Therapy ◽

Α Subunit ◽

Endocrine Disease ◽

Increased Risk ◽

Gh Receptor Antagonist ◽

Long Acting

Acromegaly is predominantly caused by a pituitary adenoma, which secretes an excess of GH resulting in increased IGF1 levels. Most of the GH assays used currently measure only the levels of the 22 kDa form of GH. In theory, the diagnostic sensitivity may be lower compared with the previous assays, which have used polyclonal antibodies. Many GH-secreting adenomas are plurihormonal and may co-secrete prolactin, TSH and α-subunit. Hyperprolactinaemia is found in 30–40% of patients with acromegaly, and hyperprolactinaemia may occasionally be diagnosed before acromegaly is apparent. Although trans-sphenoidal surgery of a GH-secreting adenoma remains the first treatment at most centres, the role of somatostatin analogues, octreotide long-acting repeatable and lanreotide Autogel as primary therapy is still the subject of some debate. Although the normalisation of GH and IGF1 levels is the main objective in all patients with acromegaly, GH and IGF1 levels may be discordant, especially during somatostatin analogue therapy. This discordance usually takes the form of high GH levels and an IGF1 level towards the upper limit of the normal range. Pasireotide, a new somatostatin analogue, may be more efficacious in some patients, but the drug has not yet been registered for acromegaly. Papers published on pasireotide have reported an increased risk of diabetes mellitus due to a reduction in insulin levels. Pegvisomant, the GH receptor antagonist, is indicated – alone or in combination with a somatostatin analogue – in most patients who fail to enter remission on a somatostatin analogue. Dopamine-D2-agonists may be effective as monotherapy in a few patients, but it may prove necessary to apply combination therapy involving a somatostatin analogue and/or pegvisomant.

Download Full-text

THYROID STIMULATORS AND THYROID STIMULATION

Acta Endocrinologica ◽

10.1530/acta.0.0660558 ◽

1971 ◽

Vol 66 (3) ◽

pp. 558-576 ◽

Cited By ~ 15

Author(s):

Gerald Burke

Keyword(s):

Regulatory System ◽

Control Site ◽

Thyroid Cell ◽

Primary Control ◽

Physico Chemical ◽

Site Of Action ◽

Long Acting

ABSTRACT A long-acting thyroid stimulator (LATS), distinct from pituitary thyrotrophin (TSH), is found in the serum of some patients with Graves' disease. Despite the marked physico-chemical and immunologic differences between the two stimulators, both in vivo and in vitro studies indicate that LATS and TSH act on the same thyroidal site(s) and that such stimulation does not require penetration of the thyroid cell. Although resorption of colloid and secretion of thyroid hormone are early responses to both TSH and LATS, available evidence reveals no basic metabolic pathway which must be activated by these hormones in order for iodination reactions to occur. Cyclic 3′, 5′-AMP appears to mediate TSH and LATS effects on iodination reactions but the role of this compound in activating thyroidal intermediary metabolism is less clear. Based on the evidence reviewed herein, it is suggested that the primary site of action of thyroid stimulators is at the cell membrane and that beyond the(se) primary control site(s), there exists a multifaceted regulatory system for thyroid hormonogenesis and cell growth.

Download Full-text

Effect of the Long-Acting Somatostatin Analogue SMS 201–995 on Small-Intestinal Interdigestive Motility in the Dog

Scandinavian Journal of Gastroenterology ◽

10.3109/00365528809090758 ◽

1988 ◽

Vol 23 (7) ◽

pp. 769-774 ◽

Cited By ~ 11

Author(s):

T. L. Peeters ◽

K. W. Romanski ◽

J. Janssens ◽

G. Vantrappen

Keyword(s):

Somatostatin Analogue ◽

Small Intestinal ◽

Long Acting ◽

Interdigestive Motility

Download Full-text

Successful treatment with a long-acting somatostatin analogue(SMS201-995) in a patient with malignant carcinoid syndrome.

Japanese Journal of Medicine ◽

10.2169/internalmedicine1962.27.311 ◽

1988 ◽

Vol 27 (3) ◽

pp. 311-316 ◽

Cited By ~ 1

Author(s):

Masayuki TSUDA ◽

Shigehisa TAMAKI ◽

Eiichi IWASAKI ◽

Seikou MURASHIMA ◽

Katsumi DEGUCHI ◽

...

Keyword(s):

Successful Treatment ◽

Carcinoid Syndrome ◽

Somatostatin Analogue ◽

Malignant Carcinoid ◽

Malignant Carcinoid Syndrome ◽

Long Acting

Download Full-text

Effective Therapy of Insulinoma by Using Long-Acting Somatostatin Analogue. A Case Report and Literature Review

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0031-1287792 ◽

2011 ◽

Vol 120 (02) ◽

pp. 68-72 ◽

Cited By ~ 10

Author(s):

A. Jawiarczyk ◽

M. Bolanowski ◽

J. Syrycka ◽

G. Bednarek-Tupikowska ◽

M. Kałużny ◽

...

Keyword(s):

Adrenal Gland ◽

Somatostatin Receptors ◽

Subcutaneous Administration ◽

Pancreatic Neuroendocrine Tumor ◽

Somatostatin Analogue ◽

Left Adrenal Gland ◽

Glucose Levels ◽

Long Acting ◽

The Right

AbstractWe are reporting a case of 68-year-old woman with insulinoma, after a non-successful tumor surgery and a long-term diazoxide treatment. She had a lot of hypoglycemia cases, and a weight gain of 50 kg. An abdominal CT scan demonstrated a tumor 28 mm in the diameter, in the head of the pancreas. The patient did not agree for the repeated insulinoma surgery. Furthermore, we found a lesion in the left adrenal gland (14 mm in the diameter) and in the right lung (8 mm in the diameter). Pheochromocytoma was diagnosed on the basis of hypertension, elevated levels of normetanephrine in the 24-h urine collection, and an elevated level of norepinephrine in a plasma sample. After the left adrenal gland removal we observed lower blood pressure. Since we had revealed the presence of somatostatin receptors by the somatostatin receptors scintigraphy, we decided to control hypoglycemia by a monthly subcutaneous administration of the long-acting lanreotide. Because of higher glucose levels (300–400 mg/dl) we started an intense insulin therapy. Nowadays, the patient feels better, she has lost 20 kg of her body weight, and we have observed normal blood glucose levels during the long-term lanreotide treatment. We have noticed neither side effects nor hypoglycemic episodes and we have reduced the dose of insulin. The presented case can be an evidence of the effective treatment of the pancreatic neuroendocrine tumor of insulinoma type, with somatostatin analogue.

Download Full-text

Cortistatin Is Not a Somatostatin Analogue but Stimulates Prolactin Release and Inhibits GH and ACTH in a Gender-Dependent Fashion: Potential Role of Ghrelin

Endocrinology ◽

10.1210/en.2011-1542 ◽

2011 ◽

Vol 152 (12) ◽

pp. 4800-4812 ◽

Cited By ~ 40

Author(s):

José Córdoba-Chacón ◽

Manuel D. Gahete ◽

Ana I. Pozo-Salas ◽

Antonio J. Martínez-Fuentes ◽

Luis de Lecea ◽

...

Keyword(s):

Metabolic Phenotype ◽

Somatostatin Analogue ◽

Growth Hormone Secretagogue Receptor ◽

Growth Hormone Secretagogue ◽

Ancestral Gene ◽

Ghrelin Receptor ◽

Physiological Relevance

Cortistatin (CST) and somatostatin (SST) evolve from a common ancestral gene and share remarkable structural, pharmacological, and functional homologies. Although CST has been considered as a natural SST-analogue acting through their shared receptors (SST receptors 1–5), emerging evidence indicates that these peptides might in fact exert unique roles via selective receptors [e.g. CST, not SST, binds ghrelin receptor growth hormone secretagogue receptor type 1a (GHS-R1a)]. To determine whether the role of endogenous CST is different from SST, we characterized the endocrine-metabolic phenotype of male/female CST null mice (cort−/−) at hypothalamic-pituitary-systemic (pancreas-stomach-adrenal-liver) levels. Also, CST effects on hormone expression/secretion were evaluated in primary pituitary cell cultures from male/female mice and female primates (baboons). Specifically, CST exerted an unexpected stimulatory role on prolactin (PRL) secretion, because both male/female cort−/− mice had reduced PRL levels, and CST treatment (in vivo and in vitro) increased PRL secretion, which could be blocked by a GHS-R1a antagonist in vitro and likely relates to the decreased success of female cort−/− in first-litter pup care at weaning. In contrast, CST inhibited GH and adrenocorticotropin-hormone axes in a gender-dependent fashion. In addition, a rise in acylated ghrelin levels was observed in female cort−/− mice, which were associated with an increase in stomach ghrelin/ghrelin O-acyl transferase expression. Finally, CST deficit uncovered a gender-dependent role of this peptide in the regulation of glucose-insulin homeostasis, because male, but not female, cort−/− mice developed insulin resistance. The fact that these actions are not mimicked by SST and are strongly gender dependent offers new grounds to investigate the hitherto underestimated physiological relevance of CST in the regulation of physiological/metabolic processes.

Download Full-text