Scientific letter
Octreotide-induced sinus bradycardia in a male patient with acromegaly
Bradicardia sinusal inducida por octreotide en un varón con acromegalia
a Unidad de Endocrinología, Instituto Autónomo Hospital Universitario de los Andes, Mérida, Venezuela
b Departamento de Ciencias Fisiológicas, Universidad de Oriente - Núcleo Bolívar, Ciudad Bolívar, Venezuela
c Instituto de Investigaciones Cardiovasculares, Departamento de Medicina, Instituto Autónomo Hospital Universitario de los Andes, Mérida, Venezuela
d Servicio de Neurocirugía, Sección de Neuroendocrinología, Departamento Quirúrgico, Hospital Clínico Universitario de Caracas, Caracas, Venezuela
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"apellidos" => "Lima-Martínez" "email" => array:1 [ 0 => "marcoslimamedical@hotmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Gabriel" "apellidos" => "López-Méndez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "Ruth" "apellidos" => "Mangupli" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Unidad de Endocrinología, Instituto Autónomo Hospital Universitario de los Andes, Mérida, Venezuela" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Ciencias Fisiológicas, Universidad de Oriente - Núcleo Bolívar, Ciudad Bolívar, Venezuela" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Instituto de Investigaciones Cardiovasculares, Departamento de Medicina, Instituto Autónomo Hospital Universitario de los Andes, Mérida, Venezuela" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Neurocirugía, Sección de Neuroendocrinología, Departamento Quirúrgico, Hospital Clínico Universitario de Caracas, Caracas, Venezuela" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Bradicardia sinusal inducida por octreotide en un varón con acromegalia" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1529 "Ancho" => 1860 "Tamanyo" => 819481 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Twenty-four-hour Holter monitoring showing the occurrence of sinus bradycardia at different times of the day.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Acromegaly is a disease characterized by excess growth hormone (GH), starting after the closure of the epiphyseal plates of long bones. Somatostatin is a peptide hormone with a short half-life (2–3<span class="elsevierStyleHsp" style=""></span>min) which is synthesized in multiple tissues, including the hypothalamus, to inhibit GH secretion. This hormone mediates its actions through five receptor subtypes (SSRs), of which SSR2 and SSR5 are the most widely expressed in pituitary adenomas.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Octreotide is a synthetic analog of somatostatin with an inhibitory action on the secretion of GH and various gastrointestinal and pancreatic hormones.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 37-year-old male patient from Mérida (Venezuela) with no personal or familial pathological history who was referred to the endocrinology unit for physiognomic changes over the previous seven years, highly severe holocranial headache, and bitemporal heteronymous hemianopsia starting five months before.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The physical examination findings included: a body weight of 102<span class="elsevierStyleHsp" style=""></span>kg, a height of 185.0<span class="elsevierStyleHsp" style=""></span>cm, a body mass index (BMI) of 29.8<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>, a heart rate of 72<span class="elsevierStyleHsp" style=""></span>bpm, blood pressure of 130/80<span class="elsevierStyleHsp" style=""></span>mmHg, and coarse facial features characterized by nose enlargement, prognathism, bulging of the forehead, and prominent cheeks. Thick skin with an oily texture, upper thoracic lordosis with compensatory lumbar hyperlordosis, prominence of the lower part of the sternum, and big hands and feet were also found, and confrontation campimetry showed bitemporal heteronymous hemianopsia. No cardiovascular or respiratory changes were found.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Laboratory tests revealed no hematological changes. Blood chemistry showed normal glucose, kidney and liver function, calcium, and phosphorus levels. Additional test results included: basal plasma GH, 9.7<span class="elsevierStyleHsp" style=""></span>μg/L (NR, 0–2.5); GH 2<span class="elsevierStyleHsp" style=""></span>h after a 75<span class="elsevierStyleHsp" style=""></span>g oral glucose tolerance test, 8.2<span class="elsevierStyleHsp" style=""></span>μg/L (NR, less than 1); IGF-1 (insulin-like growth factor), 355<span class="elsevierStyleHsp" style=""></span>ng/mL (NR for age, 109–284); thyroid-stimulating hormone (TSH), 2.45<span class="elsevierStyleHsp" style=""></span>μIU/mL (NR, 0.3–4.2); free thyroxine (FT4), 1.20<span class="elsevierStyleHsp" style=""></span>ng/dL (NR, 0.8–2); and prolactin, 12.8<span class="elsevierStyleHsp" style=""></span>ng/mL (NR in males, 0–15). Magnetic resonance imaging with gadolinium contrast revealed a pituitary macroadenoma with suprasellar extension and optic chiasm compression (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Acromegaly was diagnosed based on the clinical, laboratory, and imaging findings, and surgery was performed, but only partial resection of the pituitary macroadenoma could be performed. The patient was assessed again at three months. He reported significant improvements in headache and visual field disturbances, and was found to have a basal GH level of 3.2<span class="elsevierStyleHsp" style=""></span>μg/L and a plasma IGF-1 level of 298<span class="elsevierStyleHsp" style=""></span>ng/mL. Thus, since the biochemical criteria for disease control had not been met, treatment with octreotide 100<span class="elsevierStyleHsp" style=""></span>μg by the subcutaneous route every 8<span class="elsevierStyleHsp" style=""></span>h was prescribed, but after 10 days the patient started to experience dizziness and generalized weakness, and a physical examination revealed a heart rate of 41<span class="elsevierStyleHsp" style=""></span>bpm.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The patient was referred to the cardiology department, where 24-h Holter monitoring revealed sinus bradycardia (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>) with a mean heart rate of 44<span class="elsevierStyleHsp" style=""></span>bpm. Octreotide was discontinued, and his heart rate normalized.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Somatostatin analogs are the main therapeutic agents for the management of acromegaly.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> They have traditionally been used as an adjuvant therapy in the event of surgery failure in order to achieve biochemical control and to decrease tumor volume, as well as to provide partial or total disease control from the time of the administration of radiotherapy to the start of the maximum benefit derived from it.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The use of these agents as first-line drugs for pituitary macroadenomas with suprasellar extension to decrease tumor volume before surgery has also been postulated.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> However, they were not prescribed for this purpose in our patient due to the presence of compression signs indicating immediate surgery.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Various factors possibly accounting for the individual response to somatostatin analogs have been proposed, including: age and sex, GH levels before treatment, the GH suppression test, histopathology (tumors with dense granulation), immunohistochemical detection of SSR2, the presence of the gsp oncogene, and treatment dosage and duration.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The adverse effects most commonly associated with somatostatin analogs are gastrointestinal in nature and include nausea, vomiting, flatulence, and diarrhea. They are of variable severity and often resolve upon drug discontinuation.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Octreotide-induced bradycardia has previously been reported as an unusual finding in different clinical situations.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,6</span></a> As in our case, Herrington et al.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> reported a patient who experienced sinus bradycardia (38<span class="elsevierStyleHsp" style=""></span>bpm) after subcutaneous octreotide administration. Moreover, a significant decrease in heart rate with a concomitant increase in peripheral vascular resistance was reported in a small patient series.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The most plausible mechanism to explain the negative chronotropic effect of octreotide is the direct action of somatostatin on the heart. Somatostatin coexists with acetylcholine in presynaptic vagal endings, and may therefore be released by vagus nerve stimulation.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The main cardiovascular effects of somatostatin include decreases in heart rate and myocardial contractility and a slowing of cardiac conduction velocity. Many actions of somatostatin or its analogs result from interaction with SSRs, which belong to the family of G protein-coupled receptors and whose activation causes the inhibition of adenylate cyclase with a resultant decrease in the intracellular concentration of cyclic adenosine monophosphate (cAMP) which causes decreased conduction through voltage-dependent calcium channels and increased membrane permeability to potassium.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> In fact, because of its negative chronotropic effect and its ability to prolong atrioventricular conduction, somatostatin has been successfully used to treat supraventricular tachycardia.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">We conclude that sinus bradycardia was due to the use of octreotide, as was shown by a clear and consistent time sequence in both symptom occurrence and clinical improvement upon drug discontinuation. This potential side effect should therefore be considered when treating patients with acromegaly who require the use of somatostatin analogs.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2012-08-09" "fechaAceptado" => "2012-09-25" "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Lima-Martínez MM, López-Méndez G, Mangupli R. Bradicardia sinusal inducida por octreotide en un varón con acromegalia. Endocrinol Nutr. 2013;60:e7–e9.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1159 "Ancho" => 1235 "Tamanyo" => 151892 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Magnetic resonance imaging scan with gadolinium contrast. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 51 | 2 | 53 |
| 2024 September | 127 | 3 | 130 |
| 2024 August | 124 | 2 | 126 |
| 2024 July | 118 | 3 | 121 |
| 2024 June | 100 | 2 | 102 |
| 2024 May | 108 | 5 | 113 |
| 2024 April | 102 | 6 | 108 |
| 2024 March | 102 | 8 | 110 |
| 2024 February | 98 | 7 | 105 |
| 2024 January | 127 | 4 | 131 |
| 2023 December | 97 | 9 | 106 |
| 2023 November | 117 | 13 | 130 |
| 2023 October | 147 | 12 | 159 |
| 2023 September | 81 | 2 | 83 |
| 2023 August | 94 | 7 | 101 |
| 2023 July | 115 | 10 | 125 |
| 2023 June | 112 | 2 | 114 |
| 2023 May | 114 | 10 | 124 |
| 2023 April | 112 | 5 | 117 |
| 2023 March | 86 | 8 | 94 |
| 2023 February | 59 | 15 | 74 |
| 2023 January | 106 | 5 | 111 |
| 2022 December | 82 | 8 | 90 |
| 2022 November | 71 | 7 | 78 |
| 2022 October | 80 | 15 | 95 |
| 2022 September | 72 | 14 | 86 |
| 2022 August | 49 | 6 | 55 |
| 2022 July | 45 | 11 | 56 |
| 2022 June | 49 | 9 | 58 |
| 2022 May | 55 | 5 | 60 |
| 2022 April | 39 | 10 | 49 |
| 2022 March | 78 | 30 | 108 |
| 2022 February | 76 | 10 | 86 |
| 2022 January | 75 | 22 | 97 |
| 2021 December | 80 | 15 | 95 |
| 2021 November | 69 | 20 | 89 |
| 2021 October | 79 | 20 | 99 |
| 2021 September | 71 | 21 | 92 |
| 2021 August | 81 | 7 | 88 |
| 2021 July | 66 | 13 | 79 |
| 2021 June | 60 | 8 | 68 |
| 2021 May | 64 | 7 | 71 |
| 2021 April | 135 | 25 | 160 |
| 2021 March | 75 | 24 | 99 |
| 2021 February | 63 | 19 | 82 |
| 2021 January | 82 | 27 | 109 |
| 2020 December | 93 | 12 | 105 |
| 2020 November | 62 | 14 | 76 |
| 2020 October | 75 | 9 | 84 |
| 2020 September | 43 | 20 | 63 |
| 2020 August | 75 | 8 | 83 |
| 2020 July | 80 | 25 | 105 |
| 2020 June | 65 | 5 | 70 |
| 2020 May | 70 | 13 | 83 |
| 2020 April | 51 | 4 | 55 |
| 2020 March | 65 | 5 | 70 |
| 2020 February | 60 | 13 | 73 |
| 2020 January | 64 | 9 | 73 |
| 2019 December | 63 | 17 | 80 |
| 2019 November | 50 | 19 | 69 |
| 2019 October | 50 | 10 | 60 |
| 2019 September | 77 | 13 | 90 |
| 2019 August | 52 | 5 | 57 |
| 2019 July | 64 | 16 | 80 |
| 2019 June | 107 | 7 | 114 |
| 2019 May | 250 | 8 | 258 |
| 2019 April | 133 | 10 | 143 |
| 2019 March | 38 | 4 | 42 |
| 2019 February | 38 | 8 | 46 |
| 2019 January | 41 | 11 | 52 |
| 2018 December | 20 | 7 | 27 |
| 2018 November | 42 | 9 | 51 |
| 2018 October | 62 | 12 | 74 |
| 2018 September | 56 | 6 | 62 |
| 2018 August | 26 | 1 | 27 |
| 2018 July | 31 | 2 | 33 |
| 2018 June | 27 | 1 | 28 |
| 2018 May | 32 | 1 | 33 |
| 2018 April | 24 | 2 | 26 |
| 2018 March | 18 | 2 | 20 |
| 2018 February | 22 | 1 | 23 |
| 2018 January | 22 | 1 | 23 |
| 2017 December | 13 | 2 | 15 |
| 2017 November | 34 | 3 | 37 |
| 2017 October | 28 | 2 | 30 |
| 2017 September | 42 | 3 | 45 |
| 2017 August | 31 | 5 | 36 |
| 2017 July | 31 | 9 | 40 |
| 2017 June | 40 | 11 | 51 |
| 2017 May | 36 | 7 | 43 |
| 2017 April | 34 | 3 | 37 |
| 2017 March | 39 | 58 | 97 |
| 2017 February | 66 | 1 | 67 |
| 2017 January | 18 | 2 | 20 |
| 2016 December | 28 | 8 | 36 |
| 2016 November | 31 | 3 | 34 |
| 2016 October | 55 | 3 | 58 |
| 2016 September | 32 | 10 | 42 |
| 2016 August | 30 | 3 | 33 |
| 2016 July | 13 | 5 | 18 |
| 2016 June | 23 | 6 | 29 |
| 2016 May | 22 | 9 | 31 |
| 2016 April | 36 | 18 | 54 |
| 2016 March | 27 | 10 | 37 |
| 2016 February | 12 | 13 | 25 |
| 2016 January | 20 | 11 | 31 |
| 2015 December | 13 | 11 | 24 |
| 2015 November | 23 | 6 | 29 |
| 2015 October | 28 | 10 | 38 |
| 2014 July | 1 | 0 | 1 |
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