HISTORY, CURRENT ILLNESS AND PHYSICAL EXAMINATION

History
65-year-old woman. Allergy to methimazole. No known cardiovascular risk factors. No history of known heart disease.
Primary hyperthyroidism due to Graves-Basedow disease, treated with radioactive iodine (I-131). Current situation of hypothyroidism under replacement therapy.
Left breast nodule with histology compatible with solid pattern carcinoma with multifocal neuroendocrine differentiation (somatostatin and chromogranin receptors positive), undergoing conservative surgery in 2011 and sentinel node biopsy, which was negative.
Subsequent follow-up by oncology, with stability of the disease until 2014, when in the context of diarrhoeal syndrome, the diagnosis of carcinoid syndrome due to metastatic liver disease with positive gammagraphic uptake for somatostatin analogues was established. Stability by imaging studies since the start of treatment with somatostatin analogues, although an increase in analytical biomarkers that led to changes in the usual treatment.

Usual treatment: levothyroxine sodium 75 mcg orally every 24 hours, lanreotide autogel 120 mg injectable every 21 days.

Present illness
He came to the emergency department for marked swelling of the lower limbs and weight gain (5 kg) in the last month, although without greater dyspnoea than usual (on exertion).

She also reported an increase in the frequency of diarrhoeal episodes in the last 6 months, since the last oncology check-up. She denies other symptoms.

Physical examination
Conscious and oriented in time, space and person. Facial flushing. Blood pressure 125/68 mmHg. Eupneic at rest, with saturation by pulse oximetry 99% without contributions. Pulmonary auscultation: physiological vesicular murmur. Cardiac auscultation: rhythmic tones at 78 bpm, with pansystolic murmur (intensity III/VI) predominantly in the left parasternal border, which increases with inspiration. Abdominal examination: not painful on palpation, with discrete hepatomegaly, without signs of ascites. Examination of the extremities: oedema with fovea up to the middle third of the lower limbs, with preserved and symmetrical distal pulses. No acute inflammatory data.

COMPLEMENTARY TESTS
Electrocardiogram: sinus rhythm at 72 bpm. QRS axis 60o. PR interval 160 msec. QRS of normal voltage and amplitude. Minimal non-significant ST-segment underleveling in inferior leads. Corrected QT interval (Bazett) 460 msec.
Chest X-ray: slightly increased cardiothoracic index. No costophrenic sinus impingement. No infiltrates or condensation. No images suggestive of masses.
Laboratory tests (in the emergency department): mild hyperbilirubinaemia (total bilirubin 1.5 mg/dl) and hyponatraemia (Na+ 133 mmol/l). Blood count, coagulation, renal function parameters and the rest of the ionogram in normal ranges.
Laboratory tests on the hospital ward: normal thyroid hormone profile. Normal iron profile. 5-hydroxyindolacetic acid 355 μmol/orine 24 h (normal values: 10-40 μmol/orine 24 h). Chromogranin A (serum) 1697 ng/ml (normal values: up to 100 ng/ml). NT-proBNP 767 ng/ml.
Transthoracic echocardiogram: left ventricle (LV) neither dilated nor hypertrophic, with preserved global systolic function (LVEF 60%), without alterations in segmental contractility. Transmitral filling pattern with impaired relaxation (E: A 0.7). Slightly dilated left atrium (32 ml/m2). Mitral valve morphologically normal, with no organ involvement of interest or significant functional alterations. Tricuspid aortic valve, without organic involvement of interest, with jet of aortic regurgitation of central origin and direction that conditions mild aortic insufficiency. Aortic root of normal dimensions (26 mm). Proximal ascending aorta and aortic arch of normal size (28 mm and 26 mm, respectively). Right ventricle slightly dilated at mid-basal level (dimensions: basal diameter 43 mm, mid diameter 37 mm, length 68 mm, proximal outflow tract diameter 33 mm, distal outflow tract diameter 24 mm), with decreased longitudinal function parameters (TAPSE 15 mm, S" wave 9 cm/sec). Slightly dilated right atrium (area 20 cm2). Tricuspid valve with fibrosis at the leaflet level and restricted movement of the leaflets causing a central coaptation deficit and a tricuspid regurgitation jet leading to severe tricuspid regurgitation, with a maximum gradient (possible underestimation due to severity of regurgitation) of 50 mmHg. Pulmonary valve adequately visualised, with normal appearance. No evidence of shuntintracardiac. Inferior vena cava with dimensions in the upper normal range (20 mm) and inspiratory collapse greater than 50%. Trivial pericardial effusion.

Whole body gammagraphic study of somatostatin receptors: in comparison with the previous study (18 months earlier), multiple bilobular liver lesions were observed. The largest lesion (segment VII) shows an increase in volume (136 x 94 x 136 mm in anteroposterior-transverse-craniocaudal diameters, compared to 110 x 70 x 115 mm in the previous study). There were no other new lesions compared to the previous study. Conclusion: scintigraphic study compatible with progression of the disease.

CLINICAL EVOLUTION
The patient was admitted for a complete study, confirming the progression of the disease by means of a somatostatin receptor scintigraphy study. Given the clinical suspicion of cardiac involvement due to carcinoid syndrome (clinical symptoms and new onset murmur), a transthoracic echocardiographic study was requested, which revealed severe tricuspid insufficiency, confirming the diagnosis of carcinoid heart disease.
After initiation of depletive treatment with diuretics and intensification of treatment with somatostatin analogues, the patient progressed favourably, with symptomatic improvement (reduction of oedema in the lower limbs, reduction in the number of bowel movements, no episodes of hot flushes). The case was discussed in a clinical session with the participation of medical oncology and cardiology, estimating a vital prognosis of less than 12 months, and it was decided to discharge the patient from hospital with an increase in the dose of somatostatin analogues.
Despite this, the patient had a torpid subsequent evolution, with several readmissions in the following months for episodes similar to the one described, finally leading to her death.

DIAGNOSIS
Stage IV mammary neuroendocrine neoplasia.
Carcinoid syndrome with cardiac involvement (severe tricuspid insufficiency). Cardiac insufficiency of right predominance.
Exitus.
