Even if lung carcinoids have a better prognosis than other ACTH-secreting neuroendocrine tumors like small cell carcinomas, thymic carcinoids, medullary thyroid carcinomas and gastrinomas, they are a malignant disease with potential for metastases and increased mortality[
1,
10]. The present cases illustrate the dilemma between the need for morphological diagnosis of the ectopic ACTH source and control of the life-threatening hypercortisolism. A great help in our first patient was bilateral inferior petrosal sinus sampling with CRH stimulation for the differential diagnosis between pituitary and ectopic sources of ACTH[
11], even if false positive cases have been reported[
12]. There is no single diagnostic imaging technique for pulmonary carcinoid tumors. CT remains the gold standard for demonstrating abnormal mass in the chest[
13]. In our second patient, a normal MRI scanning of the sellar region and a lung tumor identified with CT indicated ectopic origin of the ACTH-producing tumor, whereas in our first patient further investigation was needed.
The usefulness of Tc-99m-SRS has been described in selected cases with success[
7] and may have advantages over
111In-pentetreotide-SRS used in our patient, with lower radiation dose and lower costs[
6]. However, the tumor was not detected in our first patient and this could be due to possible lack of somatostatin receptors in the tumor or the size being only 8mm, which is near the resolution limit of 6mm for SRS methods[
6]. FDG-PET was accessible, but this investigation did not visualize ectopic ACTH-secreting tumors that were occult[
8]. Therefore we decided to refer the patient for
11C-5-HTP-PET instead. Neuroendocrine tumors have a capacity for uptake and decarboxylation of amine precursors like 5-HPT, which can be used as a tracer for PET imaging[
5]. Compared with CT and SRS,
11C-5-HTP-PET has been shown to visualize more and smaller lesions down to 4 to 5mm[
5,
9]. Also, because of the biochemical pathway of 5-HPT, the nature of a lesion may be demonstrated (tumor, inflammation)[
5,
9] and, contrary to SRS, inflammatory lesions do not generally accumulate the tracer. In our first patient
11C-5-HTP-PET was essential for the diagnosis. The patient was only days from bilateral adrenalectomy, which is an effective treatment[
14], but it would have had left her with a remaining atypical carcinoid in the lung with a poor prognosis[
15]. We suggest that all modalities have to be used in searching for an occult ACTH-producing tumor, and in our first patient
11C-5-HTP-PET in an earlier stage had been preferable. Moreover, we did not perform any SRS or
11C-5-HTP-PET before primary surgery in the second patient as suggested by some authors[
5], which has given us more uncertainty postoperatively regarding remaining tumor.
In our department the routine procedure for pulmonary carcinoids is surgery with wedge excision aiming to save lung parenchyma. Young age, central tumor, and no nodal enlargement are highly suggestive of typical carcinoid and recent guidelines advocate no further diagnostic or staging tests beyond chest CT and bronchoscopy before resection using parenchyma-sparing techniques[
16]. However, some authors suggest that surgical removal of the lung carcinoid tumor should aim at “anatomic resection” rather than “parenchyma saving” surgery. This can be true in older patients and women who more often have small nodules with diameters of less than 5mm that are histologically similar to carcinoids (tumorlets)[
16]. Search for involved mediastinal lymph nodes should be rigorous, and a low threshold for clearing lymph nodes should be adopted also in typical carcinoids[
17]. Failure to remove all involved lymph nodes could lead to persistence or recurrence of the syndrome, and diminishes the chances of long-term survival[
15]. Serum ACTH could be used as a tumor marker to predict early recurrence. Besides ACTH, these tumors were shown to secrete a number of biologically active hormones and precursors that could cause Cushing’s syndrome. CRH, corticotrophin-like intermediate lobe peptide, ACTH precursors, and pro-opiomelanocortin were among the described factors[
18].